Descubren inmunidad al VIH/sida
Quienes no desarrollan sida producen mayores cantidades de células T
El gen HLA B57 permite a personas expuestas al VIH
México DF... El gen HLA B57 impulsa la producción de un mayor número de células T,
glóbulos blancos defensores del organismo ante patógenos invasores que se adhieren
firmemente a las porciones de la proteína del VIH, lo cual ayuda al organismo a mantener
bajo control el virus, señalaron científicos del Instituto de Tecnología de Massachusetts (MIT)
y la Universidad de Harvard.
Por medio de un modelo por computadora se demostró por qué un pequeño porcentaje de
las personas infectadas con VIH nunca desarrolla el sida. El hecho consiste en que, las
células T son capaces de reconocer a los organismos invasores, explicaron los
investigadores en un artículo publicado en la versión online de la revista Nature.
“Esa inmunidad natural, que ocurre en un reducido número de individuos se debe a la
actuación de esa secuencia de nucleótidos”, precisaron los expertos en inmunología.
Cuando una persona se infecta con VIH, por lo general en poco tiempo desarrolla el sida,
pero algunos individuos expuestos al virus, uno de cada 200, tardan o nunca desarrollan la
enfermedad, refiere el artículo.
De acuerdo con los investigadores, el hallazgo tiene implicaciones importantes para el
diseño de una vacuna contra la enfermedad. Por ejemplo, se podrían desarrollar vacunas
que provoquen la misma respuesta al VIH existente en los individuos con inmunidad natural.
Sin embargo, los expertos advirtieron que a pesar de saber el tipo de vacunas que se
puedan producir en un futuro, tomará al menos una década para que algunas de ellas estén
disponibles.
Quienes no desarrollan sida producen mayores cantidades de células T
El gen HLA B57 permite a personas expuestas al VIH
México DF... El gen HLA B57 impulsa la producción de un mayor número de células T,
glóbulos blancos defensores del organismo ante patógenos invasores que se adhieren
firmemente a las porciones de la proteína del VIH, lo cual ayuda al organismo a mantener
bajo control el virus, señalaron científicos del Instituto de Tecnología de Massachusetts (MIT)
y la Universidad de Harvard.
Por medio de un modelo por computadora se demostró por qué un pequeño porcentaje de
las personas infectadas con VIH nunca desarrolla el sida. El hecho consiste en que, las
células T son capaces de reconocer a los organismos invasores, explicaron los
investigadores en un artículo publicado en la versión online de la revista Nature.
“Esa inmunidad natural, que ocurre en un reducido número de individuos se debe a la
actuación de esa secuencia de nucleótidos”, precisaron los expertos en inmunología.
Cuando una persona se infecta con VIH, por lo general en poco tiempo desarrolla el sida,
pero algunos individuos expuestos al virus, uno de cada 200, tardan o nunca desarrollan la
enfermedad, refiere el artículo.
De acuerdo con los investigadores, el hallazgo tiene implicaciones importantes para el
diseño de una vacuna contra la enfermedad. Por ejemplo, se podrían desarrollar vacunas
que provoquen la misma respuesta al VIH existente en los individuos con inmunidad natural.
Sin embargo, los expertos advirtieron que a pesar de saber el tipo de vacunas que se
puedan producir en un futuro, tomará al menos una década para que algunas de ellas estén
disponibles.
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www.ambiente.us MAY | MAYO 2010
New Insights Into the Mystery of Natural HIV Immunity |
Findings May Have Implications for Designing Effective AIDS
Vaccine
ScienceDaily — 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 at 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.
New Insights Into the Mystery of Natural HIV Immunity |
Findings May Have Implications for Designing Effective AIDS
Vaccine
ScienceDaily — 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 at 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.
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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.
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.
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.
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.
This new knowledge, published online in
Nature on May 5, 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."
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."
Nature on May 5, 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."
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."
| . |
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.
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.
| . |
“Por ejemplo, se podría diseñar un fármaco capaz de provocar la misma respuesta al VIH, o
sea, con similar efecto a la inmunidad natural de estas personas”, sugieren en el texto los
autores al recordar que a mediados de la década de los 90, tras el hallazgo de un
mecanismo en el que una mutación del receptor de la célula bloqueaba el acceso del VIH a
ésta, culminó con el desarrollo de medicamentos antirretrovirales como el Maraviroc.
Copyright © AMBIENTE MAGAZINE. Do not reproduce without citing this source
sea, con similar efecto a la inmunidad natural de estas personas”, sugieren en el texto los
autores al recordar que a mediados de la década de los 90, tras el hallazgo de un
mecanismo en el que una mutación del receptor de la célula bloqueaba el acceso del VIH a
ésta, culminó con el desarrollo de medicamentos antirretrovirales como el Maraviroc.
Copyright © AMBIENTE MAGAZINE. Do not reproduce without citing this source
| . |