Cohen William M, Pouvelle-Moratille Sandra, Wang Xiao-Fei, Farci Sandrine, Munier Gaetan, Charron Dominique, Ménez André, Busson Marc, Maillère Bernard
Protein Engineering and Research Department, bâtiment 152, Commissariat à l'Energie Atomique Saclay, 91191 Gif sur Yvette, France.
J Immunol. 2006 May 1;176(9):5401-8. doi: 10.4049/jimmunol.176.9.5401.
HLA-DP4 alleles are carried by 75% of individuals and are the most frequent HLA II alleles worldwide. Because we have recently characterized the peptide-binding specificity of HLA-DP4 molecules, we developed a peptide-binding prediction method to identify HLA-DP4-restricted peptides in multiple Ags. CD4(+) T cell response plays a key role in the immune control of HIV infection, but few HIV-specific T cell epitopes with multi-individual specificity have been identified. They are mostly restricted to HLA-DR molecules, which are very polymorphic molecules. We therefore looked for HLA-DP4-restricted CD4(+) T cell epitopes in the whole genome of HIV. Twenty-one peptides were selected from the HXB2 HIV genome based on the prediction of binding to HLA-DP4 molecules. They were submitted to HLA-DP4-binding assays. Seventeen peptides bound to the HLA-DP401 molecule, whereas 15 peptides bound to HLA-DP402. Six peptides bound very tightly to HLA-DP401 and were investigated for their capacity to induce specific CD4(+) T cell lines in vitro using dendritic cells and CD4(+) T cells collected from eight seronegative HLA-DP4(+) donors. Four peptides from env and reverse transcriptase proteins induced in vitro-specific T cell lines restricted to HLA-DP4 molecules. Peptide-induced T cells recognized variants other than the HXB2 sequence and were stimulated by native Ags processed by immature dendritic cells. The reverse transcriptase peptide is present in 65% of the isolated HIV variants. To our knowledge, we describe the first HIV epitopes restricted to HLA-DP4 molecules.
75%的个体携带HLA - DP4等位基因，且它是全球最常见的HLA II类等位基因。由于我们最近已明确了HLA - DP4分子的肽结合特异性，因此开发了一种肽结合预测方法，以识别多种抗原中受HLA - DP4限制的肽。CD4(+) T细胞应答在HIV感染的免疫控制中起关键作用，但很少有具有多个体特异性的HIV特异性T细胞表位被识别出来。它们大多受限于HLA - DR分子，而HLA - DR分子是高度多态的分子。因此，我们在HIV全基因组中寻找受HLA - DP4限制的CD4(+) T细胞表位。基于与HLA - DP4分子结合的预测，从HXB2 HIV基因组中选择了21种肽。它们被用于HLA - DP4结合试验。17种肽与HLA - DP401分子结合，而15种肽与HLA - DP402结合。6种肽与HLA - DP401紧密结合，并使用从8名血清阴性的HLA - DP4(+)供体收集的树突状细胞和CD4(+) T细胞，在体外研究了它们诱导特异性CD4(+) T细胞系的能力。来自env和逆转录酶蛋白的4种肽在体外诱导了受HLA - DP4分子限制的特异性T细胞系。肽诱导的T细胞识别除HXB2序列以外的变体，并被未成熟树突状细胞加工的天然抗原刺激。逆转录酶肽存在于65%的分离HIV变体中。据我们所知，我们首次描述了受HLA - DP4分子限制的HIV表位。
