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International Immunology, Vol. 11, No. 8, 1351-1356, August 1999
© 1999 Japanese Society for Immunology

HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes

Frédérique-Anne Le Gal, Béatrice Riteau1, Christine Sedlik1, Iman Khalil-Daher1, Catherine Menier1, Jean Dausset2, Jean-Gérard Guillet, Edgardo D. Carosella1 and Nathalie Rouas-Freiss1

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
1 Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75475 Paris Cedex 10, France
2 CEPH-Fondation Jean Dausset, 27, rue Juliette-Dodu, 75010 Paris Cedex, France

Correspondence to: N. Rouas-Freiss

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.

Keywords: immunotolerance, killer inhibitory receptor

Transmitting editor: J.-F. Bach


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