McKinnon Lyle R, Ball T Blake, Wachihi Charles, McLaren Paul J, Waruk Jillian L M, Mao Xiaojuan, Ramdahin Sue, Anzala A Omu, Kamene Jane, Luo Ma, Fowke Keith R, Plummer Francis A
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
J Immunol. 2007 Mar 15;178(6):3750-6. doi: 10.4049/jimmunol.178.6.3750.
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.
由于不同毒株之间的表位序列差异，HIV的多样性可能会限制疫苗覆盖的广度。虽然CD8(+)T细胞HIV表位内的氨基酸替换可导致反应完全或部分消除，但这主要在效应性CD8(+)T细胞中得到证实。在一个感染HIV的肯尼亚队列中，我们证明HIV表位变体的交叉反应性在过夜干扰素-γ检测和长期增殖检测之间存在显著差异。对于大多数表位，在没有相应的过夜干扰素-γ反应以及HIV准种中不存在该变体的情况下，特定变体（而非索引肽）在增殖中更受青睐。通过细胞因子分析，大多数增殖的CD8(+)T细胞具有多功能性。在增殖（而非干扰素-γ）与CD4计数之间观察到正相关趋势。我们展示了与评估HIV候选疫苗相关的研究结果，并有助于更好地理解中枢和效应记忆CD8(+)T细胞如何耐受病毒多样性。
