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

In the present study, we demonstrate that the non-classical MHC class I mol ecule HLA-G impairs specific cytolytic T cell functions in addition to its well-established inhibition of NK lysis, The antigen-specific cytotoxic T l ymphocyte (CTL) response analyzed was mediated by CD8(+) T cells specific f or the influenza virus matrix epitope, M58-66, presented by HLA-AP, The tra nsfection of HLA-GI cDNA in target cells carrying the M58-66 epitope reduce d their lysis by these virus-specific CTL. This HLA-G-mediated inhibition o f 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 fun ctions, HLA-G appears to have an extensive role in immune tolerance.