HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes.
In the present study, we demonstrate that the non-classical MHC class I molecule HLA-G impairs specific cytolytic T cell functions in addition to its well-established inhibition of NK lysis. The antigen-specific cytotoxic T lymphocyte (CTL) response analyzed was mediated by CD8(+) T cells specific for the influenza virus matrix epitope, M58-66, presented by HLA-A2. The transfection of HLA-G1 cDNA in target cells carrying the M58-66 epitope reduced their lysis by these virus-specific CTL. This HLA-G-mediated inhibition of antigen-specific CTL lysis was (i) peptide dose dependent, (ii) reversed by blocking HLA-G with a specific mAb and (iii) still observed despite the blockade of HLA-E/CD94/NKG2A interaction. By inhibiting both CTL and NK functions, HLA-G appears to have an extensive role in immune tolerance.
Le Gal
F A
FA
Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM U445, Institut Cochin de Génétique Moléculaire, 27, rue du Faubourg St Jacques, Université René Descartes, 75014 Paris, France.
Riteau
B
B
Sedlik
C
C
Khalil-Daher
I
I
Menier
C
C
Dausset
J
J
Guillet
J G
JG
Carosella
E D
ED
Rouas-Freiss
N
N
D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D009980:Influenza A virus / Q000737:chemistry / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000276:immunology*
D000939:Epitopes; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D014763:Viral Matrix Proteins; C098952:influenza virus membrane protein (58-66)