Scanning the HIV genome for CD4+ T cell epitopes restricted to HLA-DP4, the most prevalent HLA class II molecule

被引:19
作者
Cohen, William M.
Pouvelle-Moratille, Sandra
Wang, Xiao-Fei
Farci, Sandrine
Munier, Gaetan
Charron, Dominique
Menez, Andre
Busson, Marc
Maillere, Bernard
机构
[1] CEA Saclay, Prot Engn & Res Dept, F-91191 Gif Sur Yvette, France
[2] Hop St Louis, INSERM, U396, Paris, France
关键词
D O I
10.4049/jimmunol.176.9.5401
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
HLA-DP4 alleles are carried by 75% of individuals and are the most frequent HLAII 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.
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页码:5401 / 5408
页数:8
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