HIV-1 epitope-specific CD8+ T cell responses strongly associated with delayed disease progression cross-recognize epitope variants efficiently.

TitleHIV-1 epitope-specific CD8+ T cell responses strongly associated with delayed disease progression cross-recognize epitope variants efficiently.
Publication TypePublication
Year of Publication2006
AuthorsTurnbull EL, A Lopes R, Jones NA, Cornforth D, Newton P, Aldam D, Pellegrino P, Turner J, Williams I, Wilson CM, Goepfert PA, Maini MK, Borrow P
JournalJ Immunol
Volume176
Issue10
Pagination6130-46
Date Published2006 May 15
ISSN0022-1767
KeywordsAcquired Immunodeficiency Syndrome, Adult, CD8-Positive T-Lymphocytes, Cells, Cultured, Chronic Disease, Cross-Priming, Disease Progression, Epitopes, T-Lymphocyte, Female, HIV-1, Humans, Immunodominant Epitopes, Male, Middle Aged
Abstract

<p>The ability of HIV-1-specific CD8(+) T cell responses to recognize epitope variants resulting from viral sequence variation in vivo may affect the ease with which HIV-1 can escape T cell control and impact on the rate of disease progression in HIV-1-infected humans. Here, we studied the functional cross-reactivity of CD8 responses to HIV-1 epitopes restricted by HLA class I alleles associated with differential prognosis of infection. We show that the epitope-specific responses exhibiting the most efficient cross-recognition of amino acid-substituted variants were those strongly associated with delayed progression to disease. Not all epitopes restricted by the same HLA class I allele showed similar variant cross-recognition efficiency, consistent with the hypothesis that the reported associations between particular HLA class I alleles and rate of disease progression may be due to the quality of responses to certain "critical" epitopes. Irrespective of their efficiency of functional cross-recognition, CD8(+) T cells of all HIV-1 epitope specificities examined showed focused TCR usage. Furthermore, interpatient variability in variant cross-reactivity correlated well with use of different dominant TCR Vbeta families, suggesting that flexibility is not conferred by the overall clonal breadth of the response but instead by properties of the dominant TCR(s) used for epitope recognition. A better understanding of the features of T cell responses associated with long-term control of viral replication should facilitate rational vaccine design.</p>

DOI10.4049/jimmunol.176.10.6130
Alternate JournalJ. Immunol.
PubMed ID16670322
Grant ListU01 HD040533 / HD / NICHD NIH HHS / United States
U01 HD040474 / HD / NICHD NIH HHS / United States
AI 49126 / AI / NIAID NIH HHS / United States
U01 HD 40533 / HD / NICHD NIH HHS / United States
AI 41530 / AI / NIAID NIH HHS / United States