Schmitt-Haendle Matthias, Bachmann Oliver, Harrer Ellen, Schmidt Barbara, Bäuerle Michael, Harrer Thomas
Immunodeficiency Center, Department of Medicine III, University Hospital Erlangen, Erlangen, Germany.
Viral Immunol. 2005;18(4):627-36. doi: 10.1089/vim.2005.18.627.
The cytotoxic T-lymphocytes (CTL) response to three histocompatibility leukocyte antigen (HLA)-A2-restricted CTL epitopes was investigated in a cohort of 51 HLA-A2-positive human immunodeficiency-1 (HIV-1)-infected subjects. CTL activity was evaluated by testing peptide stimulated peripheral blood mononuclear cells (PBMC) in chromium release assays. The most prevalent CTL response was directed to the RT-peptide ILKEPVHGV (IV9) recognized by 37.3%. The p17-peptide SLYNTVATL (SL9), reported to be the immunodominant epitope in chronically infected untreated patients, was recognized only by 13.7%. Only 9.8% recognized both IV9 and SL9, and none recognized the RT-peptide VIYQYMDDL (VL9). CTL activity correlated significantly with absolute CD8 T-cell counts but not with CD4 counts, viral load, or antiviral therapy. Analysis of the recognition patterns of amino acid substitutions in the IV9 epitope revealed the presence of at least four functionally different T-cell receptors (TCR) in this cohort. All analyzed mutations within the TCR recognition site of this epitope could abrogate CTL recognition by individual CTL clones, but all were fully immunogenic for other CTL clones with peptide-sensitizing capacities similar to that of IV9. Further studies should be performed to evaluate whether a convergent epitope vaccination strategy using immunogenic variants of CTL epitopes is a feasible approach to broaden the TCR repertoire and to inhibit CTL escape.
在51名人类免疫缺陷病毒1型（HIV-1）感染的HLA-A2阳性受试者队列中，研究了细胞毒性T淋巴细胞（CTL）对三种组织相容性白细胞抗原（HLA）-A2限制性CTL表位的反应。通过在铬释放试验中检测肽刺激的外周血单核细胞（PBMC）来评估CTL活性。最普遍的CTL反应针对RT肽ILKEPVHGV（IV9），有37.3%的受试者可识别该表位。据报道，p17肽SLYNTVATL（SL9）是未经治疗的慢性感染患者中的免疫显性表位，但只有13.7%的受试者能识别。只有9.8%的受试者能同时识别IV9和SL9，没有人能识别RT肽VIYQYMDDL（VL9）。CTL活性与绝对CD8 T细胞计数显著相关，但与CD4计数、病毒载量或抗病毒治疗无关。对IV9表位中氨基酸取代识别模式的分析表明，该队列中存在至少四种功能不同的T细胞受体（TCR）。该表位TCR识别位点内所有分析的突变都可消除单个CTL克隆对CTL的识别，但所有这些突变对其他具有与IV9相似肽致敏能力的CTL克隆都具有完全免疫原性。应进一步开展研究，以评估使用CTL表位免疫原性变体的趋同表位疫苗接种策略是否是一种可行的方法，以扩大TCR库并抑制CTL逃逸。
