CD8+ T-cell responses to different HIV proteins have discordant associations with viral load

Abstract

Selection of T-cell vaccine antigens for chronic persistent viral infections has been largely empirical. To define the relationship, at the population level, between the specificity of the cellular immune response and viral control for a relevant human pathogen, we performed a comprehensive analysis of the 160 dominant CD8+ T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific responses were associated with lowering viremia. Env-specific and Accessory/Regulatory protein–specific responses were associated with higher viremia. Increasing breadth of Gag-specific responses was associated with decreasing viremia and increasing Env breadth with increasing viremia. Association of the specific CD8+ T-cell response with low viremia was independent of HLA type and unrelated to epitope sequence conservation. These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation.

DOI: 10.1038/nm1520

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@article{Kiepiela2007CD8TR, title={CD8+ T-cell responses to different HIV proteins have discordant associations with viral load}, author={Photini Kiepiela and Kholiswa C. Ngumbela and Christina F. Thobakgale and Dhanwanthie Ramduth and Isobella Honeyborne and Eshia S. Moodley and Shabashini Reddy and Chantal de Pierres and Zenele Mncube and Nompumelelo P. Mkhwanazi and Karen S Bishop and Mary van der Stok and Kriebashnie Nair and Nasreen Khan and Hayley Crawford and Rebecca P Payne and Alasdair J. Leslie and Julia G. Prado and Andrew J. Prendergast and John A. Frater and Noel Denis McCarthy and Christian Brander and Gerald H. Learn and David C. Nickle and Christine M. Rousseau and Hoosen Mahomed Coovadia and James I. Mullins and David Heckerman and Bruce D. Walker and Philip J. R. Goulder}, journal={Nature Medicine}, year={2007}, volume={13}, pages={46-53} }