The role of the major histocompatibility complex in in vitro antibody responses; MHC restriction in responses involving linked recognition of antigenic determinants is not solely consequent to T cell-accessory cell restrictions

Abstract

Major histocompatibility complex (MHC) restrictions in the secondary antibody response in vitro to the soluble protein antigen trinitrophenyl keyhole limpet haemocyanin (TNP-KLH) were investigated. Experimental conditions were employed which ensured that co-operation between KLH-primed T cells and TNP-primed B cells was possible only through linked recognition of carrier and haptenic determinants. Under such conditions co-operation between T and B cells appears to be MHC-restricted. These experiments were designed to distinguish between two possible reasons for such MHC restrictions: (i) interaction between T and B cells is directly restricted by the MHC; or (ii) MHC-restricted T cell-antigen-presenting cell (APC) interactions limit generation of antibody responses and thus impose a pseudo-MHC restriction on T-B interactions. The ability of F1 APC to circumvent MHC restrictions was determined. The capacity of KLH-primed T cells from (P X Q)F1 leads to parent P and parent P leads to F1 X-irradiation bone marrow chimaeras to help TNP-primed parent P and parent Q B cells was assayed. Such T cells preferentially co-operate with parent P B cells. Addition of F1 APC from the spleen and the peritoneum did not alter the MHC restriction. Antibody responses stimulated by either high or low antigen concentrations were similarly MHC-restricted. Stimulation with antigen-pulsed F1 APC also failed to circumvent MHC restrictions. These results suggest that in this system involving linked recognition of antigenic determinants, the MHC directly restricts interactions between T and B cells.