Novel promiscuous HLA-DQ HIV Nef peptide that induces IFN-gamma-producing memory CD4+ T cells.
We describe the highly conserved sequence 56-68 of the HIV Nef protein as the first promiscuous HLA-DQ HIV-derived peptide. The Nef peptide exhibits an albeit rare capacity to bind 6 different HLA-DQ molecules whereas no binding is observed with the 10 HLA-DR molecules tested. In agreement with these data, after immunization with the Nef peptide, HLA-DQ transgenic Abeta degrees mice display a vigorous cellular and humoral response while the specific immune response of HLA-DR expressing mice is minimal. The promiscuous potentiality of the Nef 56-68 peptide in humans has been confirmed by ex vivo immunization experiments with CD4+ T cells from 14 healthy donors expressing different HLA genotypes. Nef 56-68 specific CD4+ T cells rapidly acquire a memory cell phenotype and are characterized by the preferential usage of the TCR Vbeta 6.1 gene segment and predominant production of IFN-gamma. Taken together, these data indicate that the Nef 56-68 peptide constitutes an attractive component of vaccines aiming at inducing or enhancing HIV-specific T cell immunity.
Pancré
V
V
UMR 8527, Institut de Biologie, Lille, France. Veronique.Pancre@ibl.fr
Georges
B
B
Angyalosi
G
G
Castelli
F
F
Delanoye
A
A
Delacre
M
M
Hachulla
E
E
Maillere
B
B
Bouzidi
A
A
Auriault
C
C
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002999:Clone Cells; D017124:Conserved Sequence; D015693:Gene Products, nef / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006678:HIV / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; C465642:HIV Nef peptide (58-68); D006683:HLA-DQ Antigens; D000949:Histocompatibility Antigens Class II; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma