Differential Immunogenicity of HIV‐1 Clade C Proteins in Eliciting CD8+ and CD4+ Cell Responses
Identifieur interne : 001520 ( Istex/Curation ); précédent : 001519; suivant : 001521Differential 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 WalkerSource :
- Journal of Infectious Diseases [ 0022-1899 ] ; 2005.
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.
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DOI: 10.1086/496894
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Marylyn Martina Addo<affiliation><mods:affiliation>Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;</mods:affiliation>
<wicri:noCountry code="subField">Massachusetts;</wicri:noCountry>
</affiliation>
<affiliation><mods:affiliation>Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;</mods:affiliation>
<wicri:noCountry code="subField">Massachusetts;</wicri:noCountry>
</affiliation>
<affiliation><mods:affiliation>Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;</mods:affiliation>
<wicri:noCountry code="subField">Massachusetts;</wicri:noCountry>
</affiliation>
<affiliation><mods:affiliation>Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;</mods:affiliation>
<wicri:noCountry code="subField">Massachusetts;</wicri:noCountry>
</affiliation>
Le document en format XML
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Cell Responses<ref type="fn" target="#fn1"></ref>
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<author><name sortKey="Chetty, Polan" sort="Chetty, Polan" uniqKey="Chetty P" first="Polan" last="Chetty">Polan Chetty</name>
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<author><name sortKey="Mngquandaniso, Nolwandle Cyloria" sort="Mngquandaniso, Nolwandle Cyloria" uniqKey="Mngquandaniso N" first="Nolwandle Cyloria" last="Mngquandaniso">Nolwandle Cyloria Mngquandaniso</name>
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<author><name sortKey="Nene, Nonhlanhla" sort="Nene, Nonhlanhla" uniqKey="Nene N" first="Nonhlanhla" last="Nene">Nonhlanhla Nene</name>
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<author><name sortKey="Harlow, Jason Davis" sort="Harlow, Jason Davis" uniqKey="Harlow J" first="Jason Davis" last="Harlow">Jason Davis Harlow</name>
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<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
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<author><name sortKey="Honeyborne, Isobella" sort="Honeyborne, Isobella" uniqKey="Honeyborne I" first="Isobella" last="Honeyborne">Isobella Honeyborne</name>
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<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
<wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu‐Natal, Durban</wicri:regionArea>
</affiliation>
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<author><name sortKey="Ntumba, Nelisiwe" sort="Ntumba, Nelisiwe" uniqKey="Ntumba N" first="Nelisiwe" last="Ntumba">Nelisiwe Ntumba</name>
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<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
<wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu‐Natal, Durban</wicri:regionArea>
</affiliation>
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<author><name sortKey="Gappoo, Sharika" sort="Gappoo, Sharika" uniqKey="Gappoo S" first="Sharika" last="Gappoo">Sharika Gappoo</name>
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<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
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<author><name sortKey="Henry, Chiara" sort="Henry, Chiara" uniqKey="Henry C" first="Chiara" last="Henry">Chiara Henry</name>
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<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
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</affiliation>
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<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
<wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu‐Natal, Durban</wicri:regionArea>
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<wicri:noCountry code="subField">Massachusetts;</wicri:noCountry>
</affiliation>
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<author><name sortKey="Altfeld, Marcus" sort="Altfeld, Marcus" uniqKey="Altfeld M" first="Marcus" last="Altfeld">Marcus Altfeld</name>
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<wicri:noCountry code="subField">Massachusetts;</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Brander, Christian" sort="Brander, Christian" uniqKey="Brander C" first="Christian" last="Brander">Christian Brander</name>
<affiliation><mods:affiliation>Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;</mods:affiliation>
<wicri:noCountry code="subField">Massachusetts;</wicri:noCountry>
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<author><name sortKey="Day, Cheryl" sort="Day, Cheryl" uniqKey="Day C" first="Cheryl" last="Day">Cheryl Day</name>
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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Coovadia, Hoosen" sort="Coovadia, Hoosen" uniqKey="Coovadia H" first="Hoosen" last="Coovadia">Hoosen Coovadia</name>
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<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
<wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu‐Natal, Durban</wicri:regionArea>
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<author><name sortKey="Kiepiela, Photini" sort="Kiepiela, Photini" uniqKey="Kiepiela P" first="Photini" last="Kiepiela">Photini Kiepiela</name>
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<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
<wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu‐Natal, Durban</wicri:regionArea>
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<author><name sortKey="Goulder, Philip" sort="Goulder, Philip" uniqKey="Goulder P" first="Philip" last="Goulder">Philip Goulder</name>
<affiliation><mods:affiliation>Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;</mods:affiliation>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation>Peter Medwar Building for Pathogen Research, Oxford University, Oxford, United Kingdom</mods:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Peter Medwar Building for Pathogen Research, Oxford University, Oxford</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Walker, Bruce" sort="Walker, Bruce" uniqKey="Walker B" first="Bruce" last="Walker">Bruce Walker</name>
<affiliation><mods:affiliation>Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;</mods:affiliation>
<wicri:noCountry code="subField">Massachusetts;</wicri:noCountry>
</affiliation>
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<front><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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