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.
引用
收藏
页码:5401 / 5408
页数:8
相关论文
共 44 条
  • [1] Longitudinal assessment of changes in HIV-specific effector activity in HIV-infected patients starting highly active antiretroviral therapy in primary infection
    Alter, G
    Hatzakis, G
    Tsoukas, CM
    Pelley, K
    Rouleau, D
    LeBlanc, R
    Baril, JG
    Dion, H
    Lefebvre, E
    Thomas, R
    Côté, P
    Lapointe, N
    Routy, JP
    Sékaly, RP
    Conway, B
    Bernard, NF
    [J]. JOURNAL OF IMMUNOLOGY, 2003, 171 (01) : 477 - 488
  • [2] Human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cells that proliferate in vitro detected in samples from most viremic subjects and inversely associated with plasma HIV-1 levels
    Boritz, E
    Palmer, BE
    Wilson, CC
    [J]. JOURNAL OF VIROLOGY, 2004, 78 (22) : 12638 - 12646
  • [3] Reconstitution of CD4+ T lymphocytes in HIV-infected individuals following antiretroviral therapy
    Carcelain, G
    Debré, P
    Autran, B
    [J]. CURRENT OPINION IN IMMUNOLOGY, 2001, 13 (04) : 483 - 488
  • [4] Castelli FA, 2002, J IMMUNOL, V169, P6928, DOI 10.4049/jimmunol.169.12.6928
  • [5] PRESENTATION OF AN IMMUNODOMINANT T-CELL EPITOPE OF HEPATITIS-B SURFACE-ANTIGEN BY THE HLA-DPW4 MOLECULE
    CELIS, E
    KARR, RW
    [J]. JOURNAL OF VIROLOGY, 1989, 63 (02) : 747 - 752
  • [6] CHARRON D, 1997, 12 INT HIST WORKSH C
  • [7] Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4+ T lymphocytes
    Chaux, P
    Vantomme, V
    Stroobant, V
    Thielemans, K
    Corthals, J
    Luiten, R
    Eggermont, AMM
    Boon, T
    van der Bruggen, P
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (05) : 767 - 777
  • [8] HLA-DP4 presents an immunodominant peptide from the RSV G protein to CD4 T cells
    de Graaff, PMA
    Heidema, J
    Poelen, MC
    van Dijk, MEA
    Lukens, MV
    van Gestel, SPJ
    Reinders, J
    Rozemuller, E
    Tilanus, M
    Hoogerhout, P
    van Els, CACM
    van der Most, RG
    Kimpen, JLL
    van Bleek, GM
    [J]. VIROLOGY, 2004, 326 (02) : 220 - 230
  • [9] Central memory CD4+ T cell responses in chronic HIV infection are not restored by antiretroviral therapy
    Elrefaei, M
    McElroy, MD
    Preas, CP
    Hoh, R
    Deeks, S
    Martin, J
    Cao, HY
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 173 (03) : 2184 - 2189
  • [10] FALK K, 1994, IMMUNOGENETICS, V39, P230