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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Acknowledgements
We thank P. D'Souza for discussions and guidance; the HIV Pathogenesis Program in Durban, especially N. Mngquandaniso, D. Ramduth, P. Chetty, N. Nene, N. Ntumba and C. Thobakgale, for their help in obtaining and processing samples from clade C–infected subjects; and N. Rizzo for the comparison of clade B and clade C peptides. Supported by the National Institutes of Health (N01-Al-15422, NO1-CO-12400 and R01-A1-067077) and by Los Alamos National Laboratory (la-ur-03-5892). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US government.
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Frahm, N., Kiepiela, P., Adams, S. et al. Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes. Nat Immunol 7, 173–178 (2006). https://doi.org/10.1038/ni1281
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DOI: https://doi.org/10.1038/ni1281
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