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High‐avidity, high‐IFNγ‐producing CD8 T‐cell responses following immune selection during HIV‐1 infection
Author(s) -
Keane Niamh M,
Roberts Steven G,
Almeida CoralAnn M,
Krishnan Tanya,
Chopra Abha,
Demaine Emma,
Laird Rebecca,
Tschochner Monika,
Carlson Jonathan M,
Mallal Simon,
Heckerman David,
James Ian,
John Mina
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.34
Subject(s) - epitope , immunodominance , biology , virology , avidity , immune system , cytotoxic t cell , immunology , human leukocyte antigen , t cell , population , cd8 , antigen , genetics , medicine , in vitro , environmental health
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 IFNγ 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.