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* Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada;
Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya; and
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
HIV diversity may limit the breadth of vaccine coverage due to epitope sequence differences between strains. Although amino acid substitutions within CD8+ T cell HIV epitopes can result in complete or partial abrogation of responses, this has primarily been demonstrated in effector CD8+ T cells. In an HIV-infected Kenyan cohort, we demonstrate that the cross-reactivity of HIV epitope variants differs dramatically between overnight IFN-
and longer-term proliferation assays. For most epitopes, particular variants (not the index peptide) were preferred in proliferation in the absence of corresponding overnight IFN- responses and in the absence of the variant in the HIV quasispecies. Most proliferating CD8+ T cells were polyfunctional via cytokine analyses. A trend to positive correlation was observed between proliferation (but not IFN-) and CD4 counts. We present findings relevant to the assessment of HIV vaccine candidates and toward a better understanding of how viral diversity is tolerated by central and effector memory CD8+ T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the National Institutes of Health (R01 AI56980 A1) and the Canadian Institutes of Health Research (HOP-43135) (to F.A.P.). F.A.P. is a Tier I Canada Research Chair in Susceptibility and Resistance to Infection. K.R.F. is supported by a National Salary Award from Canadian Institutes of Health Research. L.R.M., P.J.M., and J.L.M.W. were supported by the Canadian Institutes of Health Research and University of Manitoba Canadian Institutes of Health Research/International Center for Infectious Diseases National Training Program.
2 Address correspondence and reprint requests to Dr. T. Blake Ball, Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0W3. E-mail address: tball{at}cc.umanitoba.ca
3 Abbreviations used in this paper: Tem, effector memory CD8+ T cell; Tcm, central memory CD8+ T cell; SEB, Staphylococcus aureus enterotoxin B; SFU, spot-forming unit.
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