title: Scanning the HIV genome for CD4+ T cell epitopes restricted to HLA-DP4, the most prevalent HLA class II molecule.
abstract: 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.
authors.affiliation: Protein Engineering and Research Department, bâtiment 152, Commissariat à l'Energie Atomique Saclay, 91191 Gif sur Yvette, France.
authors.forename: William M
authors.initials: WM
authors.lastname: Cohen
authors.forename: Sandra
authors.initials: S
authors.lastname: Pouvelle-Moratille
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Wang
authors.forename: Sandrine
authors.initials: S
authors.lastname: Farci
authors.forename: Gaetan
authors.initials: G
authors.lastname: Munier
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: André
authors.initials: A
authors.lastname: Ménez
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillère
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation / Q000235:genetics; D016679:Genome, Viral / Q000235:genetics*; D006682:HLA-DP Antigens / Q000737:chemistry / Q000276:immunology*; D059868:HLA-DP beta-Chains; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D014760:Viral Fusion Proteins / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C056284:HLA-DPw4 antigen; D014760:Viral Fusion Proteins