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.
Sullivan CP., Kenny G., Waldmann H.
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.