T lymphocyte-mediated cytolysis. II. Role of target cell histocompatibility antigens in recognition and lysis.
Although compelling genetic and serologic evidence implicate target cell (TC) MHC antigens in specific cytotoxic T lymphocyte (CTL)-TC interaction leading to lysis, it is not entirely clear whether TC recognition through an MHC determinant(s) is a prerequisite for lysis to occur. In fact the finding that both specific and nonspecific TC are lysed equally well in lectin-dependent cell-mediated cytotoxicity (LDCC) challenges the necessity for TC MHC involvement in the cytolytic process beyond providing the basis for specificity in direct (nonlectin-dependent) CTL-mediated lysis. In the present paper we present evidence suggesting that even in nonspecific LDCC, as well as in nonspecific lymphocyte-mediated lysis of TC oxidized by periodate treatment or by galactose oxidase (ODCC), TC MHC components are required for lytic interactions with cytotoxic effector cells. This conclusion is based on 3 types of experimental evidence: 1) cells displaying reduced amounts of MHC proteins are poor targets in LDCC; 2) removal of H-2 by papain renders murine target cells refractory to lysis in LDCC, even though Con A binding is only slightly reduced; 3) antisera to target cell H-2-coded products block lysis in both LDCC and ODCC, whereas antisera to other cell surface antigens do not. A theory explaining nonspecific effector target interaction leading to lysis based on involvement of CTL receptor(s) and TC MHC components is presented.
D000818:Animals; D002645:Chickens; D003602:Cytotoxicity, Immunologic; D004912:Erythrocytes / Q000276:immunology; D005692:Galactose Oxidase / Q000494:pharmacology; D006183:H-2 Antigens / Q000276:immunology; D006649:Histocompatibility Antigens; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007518:Isoantibodies; D037102:Lectins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009439:Neuraminidase / Q000494:pharmacology; D010206:Papain / Q000494:pharmacology; D010504:Periodic Acid / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D007106:Immune Sera; D007518:Isoantibodies; D037102:Lectins; D010504:Periodic Acid; D005692:Galactose Oxidase; D009439:Neuraminidase; D010206:Papain