Epitope cross-reactivity frequently differs between central and effector memory HIV-specific CD8+ T cells.
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-gamma 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-gamma 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-gamma) 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.
McKinnon
Lyle R
LR
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Ball
T Blake
TB
Wachihi
Charles
C
McLaren
Paul J
PJ
Waruk
Jillian L M
JL
Mao
Xiaojuan
X
Ramdahin
Sue
S
Anzala
A Omu
AO
Kamene
Jane
J
Luo
Ma
M
Fowke
Keith R
KR
Plummer
Francis A
FA
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000328:Adult; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D015331:Cohort Studies; D003429:Cross Reactions / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D007630:Kenya; D008875:Middle Aged
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma