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.
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.
F A
FA
Le Gal
B
B
Riteau
C
C
Sedlik
I
I
Khalil-Daher
C
C
Menier
J
J
Dausset
J G
JG
Guillet
E D
ED
Carosella
N
N
Rouas-Freiss
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)