Human cell-mediated cytotoxicity against modified target cells is restricted by HLA

Abstract

T-CELL-mediated lysis of virus-infected target cells in mice is restricted by the H–2D and H–2K antigens of the major histocompatibility complex (MHC) in the sense that the cytotoxic T cells are only active against virus-infected target cells sharing H–2D and/or H–2K antigens with the animal in which the killer cells have been raised¹. These findings led to a better understanding of the way in which the MHC regulates certain functions of the immune system², and they have been amply confirmed by further studies in inbred strains of mice and guinea pig which have indicated that restriction by antigens of the MHC is a general phenomenon in the T-cell-mediated immune response³ in these species. Evidence for MHC restriction of the immune response in man, however, was lacking until it was shown that a female patient who had rejected a bone marrow graft from her HLA-identical brother, had cytotoxic cells in her blood, and that the activity of these cells was restricted to male target cells which had the HLA-A2 antigen in common with herself⁴. We show here in a more general way, that the cell-mediated cytotoxicity which can be raised in humans against ‘altered self’ is restricted by the HLA-A, B and C antigens.