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Saturday, May 15, 2010

Cubans march against homophobia


A photographer takes a picture of Farah arriving to La Rampa theater for events leading up to the International Day Against Homophobia in Havana, Saturday, May 15, 2010. International Day Against Homophobia is celebrated annually on May 17. (AP Photo/Franklin Reyes)


Members of Giganteria theater group participate in events leading up to the International Day Against Homophobia at La Rampa cinema in Havana, Saturday, May 15, 2010. International Day Against Homophobia is celebrated annually on May 17. (AP Photo/Franklin Reyes)

Mariela Castro, daughter of Cuba's President Raul Castro, front row second from right, participates in events leading up to the International Day Against Homophobia in Havana, Saturday, May 15, 2010. International Day Against Homophobia is celebrated annually on May 17. Mariela Castro directs the National Sexual Education Center. (AP Photo/Franklin Reyes)


By ANDREA RODRIGUEZ (AP)

HAVANA — Hundreds of gay and lesbian activists, some dressed in drag and others sporting multicolored flags representing sexual diversity, marched and danced through the streets of Havana on Saturday along with the daughter of Cuban President Raul Castro as part of a celebration aimed at eliminating homophobia around the world.

Some of the marchers played drums and others walked on stilts as they made their way down a wide avenue in the capital's hip Vedado neighborhood, where they have held a series of debates and workshops ahead of the May 17 celebration of the International Day Against Homophobia, which participants say marks the day in 1990 when the World Health Organization stopped listing homosexuality as a mental illness.

"We have made progress, but we need to make more progress," said Mariela Castro, a campaigner for gay rights on the island and the leader of Cuba's National Sexual Education Center. She is also the daughter of Cuban President Raul Castro.

Cuba has come a long way in accepting homosexuality. In the 1960s, shortly after the revolution, homosexuals were fired from state jobs and many were imprisoned or sent to work camps. Others fled into exile.

But that began to change in the 1980s, in large part to the work of Mariela Castro's center. Recently, the government has even agreed to include sex change operations for transsexuals under its free national health system, another project championed by the center.

The workshops and debates held Saturday dealt with issues such as adoption by gay and lesbian couples and whether to legalize gay marriages, a step Mariela Castro has been pushing for years, so far without success. The week of celebrations culminates Monday

Friday, May 14, 2010

Five Myths that Hurt Intersex People

The Intersex Roadshow:

Myth 1: Intersex people all have intermediate genitalia

Imagine this: you're an intersex person, nervous about dating and finding a partner. You work up your courage to disclose your status to people you're interested in, and after a series of them seeming polite but disinterested in dating, you finally meet a guy who expresses interest. You date for a while, and get to the point where the clothes come off. Your boyfriend gets a good look at you naked, accuses you of "making up that story of being intersex" because your body looks female to him, and breaks off the relationship, leaving you feeling misunderstood and ill-used.

Many people are intersexed in ways that are not visible to their partners. For example, an individual with AIS (androgen insensitivity syndrome) is born with internal testes but genitalia that look typically female. Intersex people born with visibly intermediate genitals are often subject to infant sex assignment surgery, another reason why our bodies may not appear visibly intersex to others.

What disturbs me about incidents in which a partner seems interested in dating an intersex person until the clothes come off is that it generally reveals that the partner was fetishizing the intersex person--only interested in them for their "exotic" body. In the situation described here, the boyfriend wanted to have sex with someone who looked genitally intermediate generally. I've also heard stories from intersex people whose genitals are visibly atypical about how a partner lost interest in them when the clothes came off because they didn't see the kind of "hermaphrodite" genitals they'd dreamt of, with a big penis and a vagina (a configuration almost unheard of in real life, but popular in pornographic fantasy). It's depressing to find out your date wasn't really interested in you, but in playing with some fantasy set of genitalia.

Myth 2: Intersex conditions are always diagnosed in infancy

Here's another unfortunate scenario: a person is having infertility problems, so they visit some doctors. They receive a diagnosis and turn in shock to an online gender forum to post "I was just diagnosed as intersex." Somebody responds, "Stop trolling this blog. You're not really intersex--intersex people all know what they are from childhood. You probably have sick fantasies or think saying you're intersex will give you an excuse to gender transition without controversy." The non-intersex person is accusing the intersex individual of being a non-intersex person exploiting intersex individuals, which is pretty ironic.

As noted above, many intersex conditions aren't obviously visible in external genitalia. That means that people may not find out about their intersex status until quite late in life. While the experiences of late-recognized intersex people are different from those of intersex folks diagnosed in infancy, they are not "less" intersex, and have to deal with physical and psychological ramifications for which they need support.

Myth 3: All infant sex-assignment surgery is aimed at creating "female" genitalia

Imagine this situation: you were born with intermediate genitalia but surgically assigned male at birth. However, you grew up hating your male sex assignment, and so you transitioned to female. Your experience has given you a lot of empathy for people viewed as gendertransgressive, so when you notice that a friend of a Facebook friend identifies as genderqueer, you write her a nice message and offer her friendship. She refuses your offer and writes you a nasty note back about how she knows you are lying about being intersex, since "all intersex children are made into girls." She accuses you of being a stalking, posing, creepy man-in-a-dress. Ironic and sad, isn't it--that a woman who identifies as breaking down the boundaries of sex and gender is policing those boundaries so rabidly and wrongheadedly?

It is true that intersex infants are disproportionately surgically assigned female, based on the appalling medical aphorism, "it's easier to make a hole than a pole." But some intersex infants are surgically assigned male--usually when they have at least one external testis, but sometimes under other conditions. The myth that this "never happens" leaves intersex people assigned male at birth open to constant suspicion and exclusion, increasing the difficulties they have to face.

Myth 4: Intersex people should be genderqueer

This myth comes up again and again in academic, activist and feminist circles: that intersex people, being neither male nor female in physical sex, must be genderqueer and androgynous. We're supposed to be standard-bearers for the fight to subvert artificial dyadic gender categories. Encountering an intersex person with an ordinary and "boring" masculine or feminine gender identity who doesn't look at all androgynous, these activists express puzzlement and disappointment--and in private, speculate that the person must have some minor, mild intersex condition, so they are not "intersex enough" to be insightful.

Intersex people face pressure from doctors and families and society at large to genderconform. Facing the opposite pressure to gendertransgress--subversivism-- is just as unfair. Yes, most intersex people open enough to disclose our sex status agree that it is damaging for our society to insist that everyone must identify as male or female. But we live in a society that understands gender dyadically, and like non-intersex people, we commonly identify as masculine or feminine.

Myth 5: "Real" intersex people are not genderqueer

Frustrated and upset by pressure from gender activists to gendertransgress, as descibed in Myth 4, some intersex people have created a reactionary opposite myth: that "real" intersex people have no interest in subverting dyadic gender understandings of male and female. These genderconservative individuals often don't actually identify as "intersex" but as "people with DSDs (Disorders of Sex Development)." And they go around arguing to institutions that "real" intersex people don't identify as genderqueer--that people who say they are intersex and argue for third gender categories and the like are posers, probably crazed feminist zealots or deceptive trans people.

What makes the myth that intersex people are never genderqueer particularly painful to me is that it is spread by members of our community. To undermine your own intersex siblings and deny their identities is counterproductive, pathetic, and cruel. Many intersex people identify as typically masculine or feminine people, but there are plenty who do not do so, and like all genderqueer people, they face a lot of social bias. We have no duty as intersex people to be genderqueer, but I see a strong moral imperative for us to support people who do have genderqueer identities and manners of selfexpression. There are enough hurtful myths circulating about intersex people already. We don't need to add one of our own to the mix.

Thursday, May 13, 2010

Theory Explains Why Some With HIV Survive Longer



A group of researchers in Boston announced a new theory this week that may help to explain a longstanding mystery in AIDS research: why some people with HIV survive for decades without ever developing AIDS.

Described in the scientific journal Nature, the research highlights the secret workings of a genetic trait that may allow some immune systems to better wage war on the virus than others. Like many new theories in science, though, it is likely to be debated -- at least one expert in the field who was not involved with the research is already cautioning that further work needs to be done.

The one thing that all experts agree upon, however, is that understanding why some people with HIV can survive longer than others has broad implications for the global epidemic. Their secrets may lead to effective vaccines against the virus, which infects more than 33 million people worldwide and kills millions of people every year.

The Mystery Of The Non-Progressors

Doctors who treat people with HIV have known for years that the virus affects people differently. Some catch it and develop AIDS very quickly, sometimes dying within a few months, while others live with HIV for a few years without symptoms, though they develop AIDS eventually. New drugs and treatment strategies have helped people live longer than ever in the last 15 years -- saving some 2.9 million lives in the past two decades, according to estimates by the Joint United Nations Program on HIV/AIDS.

About one out of every 200 people who catch HIV are considered "long-term non-progressors" or "elite controllers" because they can live for many years with the virus without developing AIDS. Even the most sensitive tests often cannot detect the virus in their bloodstream.

"Some of our patients have been infected for more than 27 years and have not had any blips or declines in their CD4+ count [a measure of progress towards AIDS]," said immunologist Mark Connors, who works with non-progressors at the National Institute of Allergy and Infectious Diseases in Bethesda, MD.

Numerous studies have followed these people, seeking to understand how their bodies control HIV so well when so many others succumb to the virus. What accounts for this difference is the crux of the new theory by the team in Boston, led by Arup Chakraborty of MIT in collaboration with Bruce Walker at Massachusetts General Hospital.

Part Genes, Part Luck

According to Chakraborty, one of the reasons why non-progressors can control HIV so well is a combination of good genes and good luck.

About half of all the people who have natural HIV resistance share a genetic trait known as "HLA-B57," a particular form of the gene that makes a molecule known as HLA. This molecule plays a part in developing the immune system's killer T cells, which seek out and destroy cells infected by HIV and other viruses.

In general, HLA helps to delete T cells that are too reactive and could cause a whole host of problems by damaging healthy tissue.

Chakraborty and his colleagues used computer simulations to study the diversity of interactions between HLA and killer T cells, and they determined that the HLA-B57 variation of the gene tends to remove fewer developing killer T cells. This creates a population of these killer T cells that are cross-reactive and may be better at fighting HIV, keeping up with the virus as it constantly mutates.

Having the HLA-B57 trait by itself is not enough for natural resistance -- 99 percent of people who have it are not non-progressors -- but for a lucky few it could lead to cross-reactive killer T cells that can recognize a wider range of HIV.

"This ability to have cross-reactive T cells gives you better control of the virus," said Chakraborty.

Some researchers, including Connors, remain unconvinced.

"It's an interesting idea, but it needs to be backed up by experimental data." he said. "There is no objective data that shows non-progressors have greater cross-reactivity."

If future studies confirm the theory and a way can be found to artificially induce such broadly-reactive killer T cells in people, researcher might be able to design a vaccine to do just that -- though there is no guarantee that such a vaccine would ultimately prove effective, as the history of AIDS vaccine trials has shown more than once.

Source: Inside Science News Service

Bruce must go, but then what? ..................

The Editor, Sir:

After listening with horror to the prime minister's confession in the Coke-Manatt affair, I immediately said, "He needs to resign!". For at least the next two hours, I was furious and saying to anyone who would listen, "Bruce needs to go."

However, after I had absorbed the news and began to think, I realised, if Bruce goes, who will replace him? In the Jamaica Labour Party (JLP), there is no one who seems to be able to lead themselves much less the country. Then I looked at the People's National Party (PNP) and realised that there was nothing to look at.

As it stands, the PNP has descended on this issue, but who in the PNP has any moral authority to speak for Jamaica? That party is no more than a party of individuals who are just conveniently banding together to gain political power.

After we chase Bruce out, what solutions are the PNP going to come with? How will they deal any differently with crime or the debt? They were the initial farmers of the downward spiral in which we find ourselves, so what difference will they make?

No honour

Bruce, you gave up your honour for a man who is too cowardly to come and face the courts himself. I could understand the issue behind the wiretap - somewhat - but now you are being made to look like a fool. Jamaica has been made to look like a country of 'shady' men.

Bruce, you have placed yourself in a corner and have nowhere to go. My advice to you, even though I am mad with you, is look toward the Almighty as there is your only hope for redemption.

I am, etc.,

DONNA SCOTT

honeywelljm@yahoo.com

Lauderdale Lakes

Florida


My two cents:
With the plethora of voices calling for The Prime Minister's resignation and all of a sudden everybody now has morality fever where were these voices when other ills faced this country?

When the Armadale fire happened and seven girls perished where was the outcry that is so loud now for blood?

Where was the outcry for rights for ALL citizens despite of race class creed or orientation? yes while I may concur that the PM has slipped up many calling now for his head are mere political john crows (not saying this letter writer is) hovering over nearly dead meat waiting for it to die and begin rotting so they can feast.

The Peoples National Party must not forget their own set of scandals and amongst their midst is one who presently is being tried for alleged embezzlement as we all know the Kern Spencer affair where Cuban light bulb money allegedly cannot be properly accounted for, lest we forget he is on tape and by the looks of it he tried to cipher off some of it by false paperwork in collusion with others. The case now dangles in court with all kinds of legal manoeuvres taking place with judicial review after judicial review and delays, justice delayed is justice denied I tell you.

Straight hypocrisy no pun intended I tell you that's what happening here amongst the real honest citizenry.

Peace and tolerance.

H

Wednesday, May 12, 2010

Jah Cure goes techno with Never Say Never ..... remember the dancehall meets house post?




Following on the post Dancehall/Reggae meets housemusic: Is Tolerance already there?
here we see a perfect fusion yet again happening with a Jamaican artist using the services of European remixer to reach bigger markets.

What the Observer Entertainment article below didn't get into is the vision of Jah Cure to enter the market through this Techno/House vein which can be used to settle the problems with the homophobic lyrics issues by local acts and The Stop Murder Music Campaigns worldwide. Tolerance in as far as the crossings of Reggae with house music in it's varying forms predominantly followed by GLBTQ people is refeshing and shows that entertainment on a whole can be the bridge to reaching some form of harmony.

Article:
Producer, Rick Warren, has remixed Jah Cure's recent hit, Never Say Never, with a Techno flavour. The reggae version of the song was released in February of this year on the Stonehenge Riddim and was the first single of that compilation.

The Stonehenge rhythm also features artistes such as Anthony B, George Nooks, Pressure, Bryan Art, Lutan Fyah, Gyptian and Courtney John among others.

Now Rick Warren has again shown his ingenuity by remixing the song. Warren reveals that the remix involves a significant amount of automation and the production is more technical that would be necessary on the reggae track.

The track for the techno version was built using Protocols. Warren says the building of a techno beat is very tedious as the finished product is focused a lot on the arrangement and less on the vocals. He says that a techno track also has a lot of other elements that would not be included on a Dancehall or Reggae track such as crescendos and filter sweeps.

"I made the electronic remix to Jah Cure's Never Say Never to open up new doors for Reggae music. I'm trying to get fans that don't normally listen to Reggae artistes and would probably never of heard of Jah Cure, to get a chance to listen to his music," Warren explained.

"I think it will be well received. Even though we changed the genre of the original song to make it more appealing to dance music fans, we still kept some Reggae elements so the hardcore Reggae fans will still appreciate it," he said.

According to Jah Cure, he is very happy that Rick decided to remix the song: "My fans in Europe don't only listen to Reggae music they also listen to House and Techno and I think that this is just another way for me to connect with them in their space".

The Techno remix of Never Say Never has been released online and is also getting rotation on several radio stations in Jamaica and the Caribbean. Warren says he will be releasing the song to European stations in the coming week as there have been several requests from that part of the world for the remix.


Tuesday, May 11, 2010

Gay asylum seekers challenge UK's policy in court, implications for other cases


Two gay men are appealing against the UK's policy on returning gay and lesbian asylum seekers to their home countries.

The cases are being heard this week in the Supreme Court, with the men, one from Cameroon and the other from Iran, appealing against previous court decisions barring them from gaining asylum.

Gay asylum campaigners argue that the UK frequently tells gay asylum seekers that they can return to homophobic countries if they are "discreet" or relocate.

The two cases will be heard separately over three days.

The Cameroonian man is appealing against a tribunal decision which could he could be sent home despite being attacked after he was seen kissing his partner.

The Iranian man was told by a tribunal that he must expect persecution for his homosexuality and could avoid it by being discreet.

Angela Mason, the patron of the UK Lesbian and Gay Immigration Group, told the Guardian: "It seems that the Home Office are routinely refusing applications on the grounds that lesbians and gay men can go back and be 'discreet' or 'relocate'.

"Decisions are being made by Home Office case owners who lack essential training on dealing with such claims … The result is that lesbian and gay asylum seekers who are already experiencing persecution may also face discrimination in our own country."

Last month, an Amnesty International report claimed that the UK and several other European countries were breaching international law on returning vulnerable Iraqi asylum seekers.

According to the report, women, ethnic minorities and gays, or those perceived to be gay, are most likely to be at risk of violence and persecution in the country.

Amnesty accused the UK, along with several other countries, of forcibly returning "scores" of Iraqis to dangerous areas in the country, breaking international rules.

Monday, May 10, 2010

Psychiatric evaluation for senior on buggery charge

Tanesha Mundle

A senior citizen, who has found himself on the wrong side of the law after allegations surfaced that he sexually assaulted a 12-year-old boy, is to undergo psychiatric evaluation to determine whether he is fit to answer to charges of buggery and gross indecency.

The 59-year-old man was remanded in custody when he appeared in the Corporate Area Resident Magistrate's Court recently, after Resident Magistrate Georgianna Fraser ruled that he is to be examined by a psychiatrist.

However, the accused, who could be seen mumbling to himself, begged the magistrate to give him bail, but it was denied.

"Not today, I need to find out whether or not you are a danger to yourself and to others," Fraser said.

According to police reports, on March 23 this year, the complainant left school about 9:00 am and went to visit the accused man, who lives in a tree.

The youth, who is a ward of the state, reportedly spent the night at the accused man's 'home' and was fondled and raped.

The man was arrested the following morning when residents saw him with the child in the community and called the police.

The juvenile reportedly informed the police of the ordeal and the man was charged.

Genital wart virus may raise men's risk of HIV suggests Kenyan study

NEW YORK (Reuters Health) - Men who carry the virus that causes genital warts may be at increased risk of HIV infection, a study of Kenyan men suggests.

Researchers say the findings raise the possibility that vaccination against the virus, known as the human papillomavirus (HPV), could help curb the world's HIV pandemic.

The investigators found that among 2,168 Kenyan men between the ages of 18 and 24, half tested positive for HPV at the start of the study. Over the next 3.5 years, nearly 6 percent of those men became infected with HIV, versus just under 4 percent of those who had tested HPV-negative at the outset.

When the researchers controlled for a number of HIV risk factors, men with HPV were still 80 percent more likely than their HPV-negative counterparts to become infected with HIV, suggesting the genital wart virus itself may boost a person's susceptibility to HIV.

The findings are published in the Journal of Infectious Diseases.

There are more than 100 strains of HPV, some of which cause genital and anal warts. In most people, the immune system clears the infection fairly rapidly. However, persistent infection with certain HPV strains can eventually lead to cancer in some cases.

Persistent HPV infection is the primary cause of cervical cancer, and it can also lead to cancers of anus and penis.

The current findings come from a larger clinical trial that, along with two other trials in Africa in 2005 and 2006, found that circumcision lowered men's risk of acquiring HIV through heterosexual sex. Subsequent studies of those men have shown that circumcision may also lower the odds of HPV infection.

In this latest study, HPV infection itself was linked to a higher risk of acquiring HIV even when the researchers factored in circumcision, as well as the men's reported sexual history and whether they had the genital herpes virus -- which has already been linked to an increased risk of HIV infection.

All of this suggests that HPV vaccination, along with circumcision, could help stem the HIV pandemic, according to lead researcher Dr. Jennifer S. Smith, of the University of North Carolina at Chapel Hill.

"Finding a vaccine to prevent HIV is the greatest hope for curbing the world's AIDS pandemic, but so far there is no such vaccine," Smith said in a written statement from the university. "However, there is a vaccine to prevent specific types of HPV infection, and vaccinating young men before they become sexually active could potentially help prevent the spread of HIV."

There are two vaccines that can prevent infection with certain cancer-related strains of HPV: Gardasil (from Merck) and Ceravix (from GlaxoSmithKline). In the U.S., the vaccines are approved for girls and young women as young as 9, and up to the age of 26. Last year, regulators approved Gardasil for boys and men in the same age group.

The current findings, according to Smith's team, warrant clinic trials to test whether HPV vaccination can lower the risk of HIV infection.

If vaccination does prove effective, cost could stand as a major obstacle to bringing it to developing nations where HIV transmission rates are high. The required three doses of the HPV vaccines cost roughly $400 in the U.S.

It's not clear why HPV infection might increase the odds of HIV infection, but it is biologically plausible, according to Smith's team. Skin lesions caused by HPV, for example, might act as "portals of HIV entry," the researchers note. In addition, HPV may induce the production of certain inflammatory proteins in the genital area, which may in turn boost susceptibility to HIV infection.

The study was funded by the U.S. National Institutes of Health and the Canadian Institutes of Health Research.

SOURCE: Journal of Infectious Diseases, June 1, 2010.

Sunday, May 9, 2010

New insights into the mystery of natural HIV immunity

A new finding from the Ragon Institute of MGH, MIT and Harvard may have implications for designing an effective AIDS vaccine.

Anne Trafton, MIT News Office

When people become infected by HIV, it’s usually only a matter of time, barring drug intervention, until they develop full-blown AIDS. However, a small number of people exposed to the virus progress very slowly to AIDS — and some never develop the disease at all.

In the late 1990s, researchers showed that a very high percentage of those naturally HIV-immune people, who represent about one in 200 infected individuals, carry a gene called HLA B57. Now a team of researchers from the Ragon Institute of Massachusetts General Hospital, MIT and Harvard has revealed a new effect that contributes to this gene’s ability to confer immunity.

The research team, led by MIT Professor Arup Chakraborty and Harvard Professor Bruce Walker of MGH, found that the HLA B57 gene causes the body to make more potent killer T cells — white blood cells that help defend the body from infectious invaders. Patients with the gene have a larger number of T cells that bind strongly to more pieces of HIV protein than people who do not have the gene. This makes the T cells more likely to recognize cells that express HIV proteins, including mutated versions that arise during infection. This effect contributes to superior control of HIV infection (and any other virus that evolves rapidly), but it also makes those people more susceptible to autoimmune diseases, in which T cells attack the body’s own cells.

This new knowledge, described in the May 5 online edition of Nature, could help researchers develop vaccines that provoke the same response to HIV that individuals with HLA B57 muster on their own, says Walker, who is director of the Ragon Institute and a professor at Harvard Medical School.

“HIV is slowly revealing itself,” says Walker. “This is another point in our favor in the fight against the virus, but we have a long way to go.”

Natural resistance

Chakraborty, a professor of chemical engineering, chemistry and biological engineering who specializes in theoretical and computational studies of the immune system, undertook this study after Walker told him about the phenomenon of HLA B57-induced immunity. Chakraborty was also intrigued by the fact that people who carry the HLA B57 gene also are more likely to develop autoimmune disorders.

Chakraborty, Walker and their colleagues focused on killer T cells, one of two types of T cells that play an important role in the immune response. Most killer T cells are genetically unique and recognize different pieces of foreign proteins, known as epitopes, attached to the surface of cells that have been infected by viruses or bacteria.

After a killer T cell grabs hold of such a protein, it becomes activated and starts sweeping the body for more cells that express the same protein, so it can kill them. It also clones itself to produce an army of T cells targeting the invader.

The new Ragon Institute study shows that individuals with the HLA B57 gene produce larger numbers of killer T cells that are cross-reactive, meaning they can attack more than one epitope associated with HIV, including mutants that arise to escape activated killer T cells.

The finding offers hope that researchers could design a vaccine to help draw out cross-reactive T cells in people who don’t have the HLA B57 gene. “It’s not that they don’t have cross-reactive T cells,” says Chakraborty. “They do have them, but they’re much rarer, and we think they might be coaxed into action with the right vaccine.”

The work is a valuable contribution to scientists’ understanding of HIV, says David Baltimore, professor of biology and former president of Caltech.

“This is a remarkable paper because it starts from a clinical observation, integrates it with experimental observations, generates a valuable model and derives from the model a deep understanding of the behavior of the human immune system. Rarely does one read a paper that stretches the mind so surprisingly far,” says Baltimore, a Nobel laureate in physiology or medicine who now studies HIV and human T cell interactions.

Weeding out

Chakraborty and colleagues had previously developed computational models of T-cell development in the thymus, an organ located behind the breastbone through which T cells must pass in order to become mature killers. There they undergo a selection process designed to weed out cells that might attack the body’s own cells (which display pieces of human proteins on their surface). T cells must also demonstrate that they can bind weakly to some human protein fragments. Only a tiny percentage of T cells pass these tests and are allowed to leave the thymus and circulate in the body to defend against viruses, other diseases, and cancerous cells.

Inside the thymus, T cells are exposed to “self-peptides” — small human protein fragments — bound to HLA proteins. Chakraborty and co-workers had previously shown that the diversity of self-peptide fragments presented in the thymus influences the kinds of T cells a person can produce. The type and number of self-peptides expressed are determined by the HLA genes, which have hundreds of distinct forms, including HLA B57. Each person carries up to six of them (three inherited from each parent).

Using data from previous studies, the Ragon team found that HLA B57 protein presents fewer types of self-peptides than most other HLA proteins. (HLA B27 is another protein that presents few types of self-peptides and also appears to protect against HIV and promote autoimmune disorders.) In this study, Chakraborty and postdoctoral fellow Elizabeth Read and graduate student Andrej Kosmrlj, lead authors of the paper, used their computer model to study what happens when maturing T cells are exposed to only a small diversity of self-peptides in the thymus.

T cells with receptors that bind strongly to any of the self-peptides in the thymus are forced to undergo cell suicide, because of their potential to attack the body’s own cells. Chakraborty and co-workers showed that this means that, for most individuals, most of the body’s T cells have receptors that bind to targeted viral proteins via a number of weak interactions, with each interaction making a significant contribution to the binding. Thus, a single mutation to an HIV peptide can potentially evade the immune response.

A different scenario unfolds in people who have the HLA B57 gene. Using their computer model, Chakraborty and colleagues showed that, because those individuals’ T cells are exposed to fewer self-peptides in the thymus, T cells with receptors that mediate strong binding to viral proteins via just a few important contacts are more likely to escape the thymus. This makes these T cells more cross-reactive to targeted HIV peptide mutants, because as long as those points in the viral proteins don’t mutate, the T cells are still effective. The model also showed that once those T cells are released into the bloodstream, they can effectively attack HIV proteins, even when the virus mutates.

This model also explains why people with the HLA B57 gene have autoimmune problems: Their T cells are more likely to bind strongly to human peptides not encountered in the thymus.

The computational studies explained many puzzles, but also made a prediction: Individuals with HLA genes that result in a display of fewer self-peptides should control HIV (and other viruses like hepatitis C virus) better. To test this prediction, the researchers studied nearly 2,000 patients — 1,100 “HIV controllers” and 800 who progressed normally to AIDS, and confirmed that this appears to be true.

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