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High-avidity, high-IFNγ-producing CD8 T-cell responses following immune selection during HIV-1 infection
Journal article   Peer reviewed

High-avidity, high-IFNγ-producing CD8 T-cell responses following immune selection during HIV-1 infection

N.M. Keane, S.G. Roberts, C.M. Almeida, T. Krishnan, A. Chopra, E. Demaine, R. Laird, M. Tschochner, J.M. Carlson, S. Mallal, …
Immunology and Cell Biology, Vol.90(2), pp.224-234
2012
DOI: https://doi.org/10.1038/icb.2011.34
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Abstract

HIV-1 mutations, which reduce or abolish CTL responses against virus-infected cells, are frequently selected in acute and chronic HIV infection. Among population HIV-1 sequences, immune selection is evident as human leukocyte antigen (HLA) allele-associated substitutions of amino acids within or near CD8 T-cell epitopes. In these cases, the non-adapted epitope is susceptible to immune recognition until an escape mutation renders the epitope less immunogenic. However, several population-based studies have independently identified HLA-associated viral changes, which lead to the formation of a new T-cell epitope, suggesting that the immune responses that these variants or 'neo-epitopes' elicit provide an evolutionary advantage to the virus rather than the host. Here, we examined the functional characteristics of eight CD8 T-cell responses that result from viral adaptation in 125 HLA-genotyped individuals with chronic HIV-1 infection. Neo-epitopes included well-characterized immunodominant epitopes restricted by common HLA alleles, and in most cases the T-cell responses against the neo-epitope showed significantly greater functional avidity and higher IFN gamma production than T cells for non-adapted epitopes, but were not more cytotoxic. Neo-epitope formation and emergence of cognate T-cell response coincident with a rise in viral load was then observed in vivo in an acutely infected individual. These findings show that HIV-1 adaptation not only abrogates the immune recognition of early targeted epitopes, but may also increase immune recognition to other epitopes, which elicit immunodominant but non-protective T-cell responses. These data have implications for immunodominance associated with polyvalent vaccines based on the diversity of chronic HIV-1 sequences.

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Collaboration types
Industry collaboration
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International collaboration
Citation topics
1 Clinical & Life Sciences
1.66 HIV
1.66.46 HIV Pathogenesis
Web Of Science research areas
Cell Biology
Immunology
ESI research areas
Immunology
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