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HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses
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نویسنده
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erdmann n. ,du v.y. ,carlson j. ,schaefer m. ,jureka a. ,sterrett s. ,yue l. ,dilernia d. ,lakhi s. ,tang j. ,sidney j. ,gilmour j. ,allen s. ,hunter e. ,heath s. ,bansal a. ,goepfert p.a.
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منبع
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plos pathogens - 2015 - دوره : 11 - شماره : 8
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چکیده
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Antiretroviral therapy,antibody and cd8+ t cell-mediated responses targeting human immunodeficiency virus-1 (hiv-1) exert selection pressure on the virus necessitating escape; however,the ability of cd4+ t cells to exert selective pressure remains unclear. using a computational approach on hiv gag/pol/nef sequences and hla-ii allelic data,we identified 29 hla-ii associated hiv sequence polymorphisms or adaptations (hla-ap) in an african cohort of chronically hiv-infected individuals. epitopes encompassing the predicted adaptation (ae) or its non-adapted (nae) version were evaluated for immunogenicity. using a cd8-depleted ifn-γ elispot assay,we determined that the magnitude of cd4+ t cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). however,regardless of the group,the magnitude of responses to ae was lower as compared to nae (p<0.0001). cd4+ t cell responses in patients with acute hiv infection (ahi) demonstrated poor immunogenicity towards ae as compared to nae encoded by their transmitted founder virus. longitudinal data in ahi off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent cd4+ escape mutations. these data demonstrate an innovative application of hla-associated polymorphisms to identify biologically relevant cd4+ epitopes and suggests cd4+ t cells are active participants in driving hiv evolution. © 2015 erdmann et al.
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آدرس
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department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, microsoft research,los angeles,ca, United States, department of pathology and laboratory medicine,emory university,atlanta,ga, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of pathology and laboratory medicine,emory university,atlanta,ga, United States, department of pathology and laboratory medicine,emory university,atlanta,ga, United States, zambia emory research project,lusaka, Zambia, department of medicine,university of alabama at birmingham,birmingham,al, United States, la jolla institute for allergy & immunology,la jolla,ca, United States, international aids vaccine institute and imperial college,london, United Kingdom, department of pathology and laboratory medicine,emory university,atlanta,ga, United States, department of pathology and laboratory medicine,emory university,atlanta,ga, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States
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Authors
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