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Differential Immunogenicity of HIV‐1 Clade C Proteins in Eliciting CD8+ and CD4+ Cell Responses

Identifieur interne : 002F40 ( Main/Exploration ); précédent : 002F39; suivant : 002F41

Differential Immunogenicity of HIV‐1 Clade C Proteins in Eliciting CD8+ and CD4+ Cell Responses

Auteurs : Danni Ramduth [Afrique du Sud] ; Polan Chetty [Afrique du Sud] ; Nolwandle Cyloria Mngquandaniso [Afrique du Sud] ; Nonhlanhla Nene [Afrique du Sud] ; Jason Davis Harlow [Afrique du Sud] ; Isobella Honeyborne [Afrique du Sud] ; Nelisiwe Ntumba [Afrique du Sud] ; Sharika Gappoo [Afrique du Sud] ; Chiara Henry [Afrique du Sud] ; Prakash Jeena [Afrique du Sud] ; Marylyn Martina Addo ; Marcus Altfeld ; Christian Brander ; Cheryl Day [Royaume-Uni] ; Hoosen Coovadia [Afrique du Sud] ; Photini Kiepiela [Afrique du Sud] ; Philip Goulder [Royaume-Uni] ; Bruce Walker

Source :

RBID : ISTEX:4222E856E5253B10486402C09E3F9AEA716D7F46

Abstract

Background. The relative immunogenicity of human immunodeficiency virus type 1 (HIV‐1) proteins for CD8+ and CD4+ cell responses has not been defined. Methods. HIV‐1–specific T cell responses were evaluated in 65 chronically HIV‐1–infected untreated subjects by interferon‐γ flow cytometry with peptides spanning the clade C consensus sequence. Results. The magnitude of HIV‐1–specific CD8+ T cell responses correlated significantly with CD4+ cell responses, but the percentage of CD8+ T cells directed against HIV‐1 (median, 2.76%) was always greater than that of CD4+ cells (median, 0.24%). Although CD8+ T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4+ cell responses. There was no consistent relationship between virus‐specific CD8+ or CD4+ cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8+ T cell target was significantly lower than that in subjects in whom non‐Gag proteins were the main target (P=.007). Conclusions. Gag‐specific responses dominate the CD4+ T cell response to HIV, whereas CD8+ T cell responses are broadly distributed, which indicates differential immunogenicity of these cells against HIV‐1. The preferential targeting of Gag by CD8+ T cells is associated with enhanced control of viral load.

Url:
DOI: 10.1086/496894


Affiliations:


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Le document en format XML

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<div type="abstract">Background. The relative immunogenicity of human immunodeficiency virus type 1 (HIV‐1) proteins for CD8+ and CD4+ cell responses has not been defined. Methods. HIV‐1–specific T cell responses were evaluated in 65 chronically HIV‐1–infected untreated subjects by interferon‐γ flow cytometry with peptides spanning the clade C consensus sequence. Results. The magnitude of HIV‐1–specific CD8+ T cell responses correlated significantly with CD4+ cell responses, but the percentage of CD8+ T cells directed against HIV‐1 (median, 2.76%) was always greater than that of CD4+ cells (median, 0.24%). Although CD8+ T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4+ cell responses. There was no consistent relationship between virus‐specific CD8+ or CD4+ cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8+ T cell target was significantly lower than that in subjects in whom non‐Gag proteins were the main target (P=.007). Conclusions. Gag‐specific responses dominate the CD4+ T cell response to HIV, whereas CD8+ T cell responses are broadly distributed, which indicates differential immunogenicity of these cells against HIV‐1. The preferential targeting of Gag by CD8+ T cells is associated with enhanced control of viral load.</div>
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