Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes - PubMed (original) (raw)

doi: 10.1038/ni1281. Epub 2005 Dec 20.

Photini Kiepiela, Sharon Adams, Caitlyn H Linde, Hannah S Hewitt, Kaori Sango, Margaret E Feeney, Marylyn M Addo, Mathias Lichterfeld, Matthew P Lahaie, Eunice Pae, Alysse G Wurcel, Timothy Roach, M Anne St John, Marcus Altfeld, Francesco M Marincola, Corey Moore, Simon Mallal, Mary Carrington, David Heckerman, Todd M Allen, James I Mullins, Bette T Korber, Philip J R Goulder, Bruce D Walker, Christian Brander

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Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes

Nicole Frahm et al. Nat Immunol. 2006 Feb.

Abstract

Despite limited data supporting the superiority of dominant over subdominant responses, immunodominant epitopes represent the preferred vaccine candidates. To address the function of subdominant responses in human immunodeficiency virus infection, we analyzed cytotoxic T lymphocyte responses restricted by HLA-B*1503, a rare allele in a cohort infected with clade B, although common in one infected with clade C. HLA-B*1503 was associated with reduced viral loads in the clade B cohort but not the clade C cohort, although both shared the immunodominant response. Clade B viral control was associated with responses to several subdominant cytotoxic T lymphocyte epitopes, whereas their clade C variants were less well recognized. These data suggest that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination of subdominant yet effective epitopes from circulating viral populations.

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