Alloantiserum-Mediated Suppression of Histocompatibility-Linked Ir Gene Controlled Immune Responses

Abstract

Abstract Alloantisera were produced in guinea pigs by immunizing one inbred strain with the lymphoid cells of another. The effect of these sera on the response of sensitized lymphocytes to antigen or mitogen was studied in vitro. Strain 13 anti-strain 2 alloantisera, when added to cultures at a 1:75 or greater dilution, specifically suppress responses to GA and to 2,4-dinitrophenyl (DNP)-GL, both of which are controlled by strain 2-linked immune response (IR) genes. Addition of the anti-strain 2 sera at higher concentrations diminishes the apparent specificity for strain 2-associated immune responses. for example, at a 1:30 dilution the anti-strain 2 sera suppress the response of sensitized Hartley lymphocytes to the mitogen phytohemagglutinin and to the antigen GT whose controlling immune response gene is linked to strain 13 histocompatibility antigens. When compared as a function of antiserum concentration, the ability of the anti-strain 2 alloantisera to suppress strain 2-associated immune responses in vitro closely parallels its cytotoxic capacity. Furthermore, the ability of the anti-strain 2 sera to suppress GA responses in vitro depends on the presence of strain 2 histocompatibility antigens on the responding lymphocytes. In contrast to its effective suppression of GA responses in sensitized lymphocytes bearing strain 2 histocompatibility antigens, the anti-strain 2 antisera has no effect on the response to GA in lymphocytes from responder Hartley guinea pigs that did not inherit the strain 2 histocompatibility locus. These studies indicate that the histocompatibility antigens on the lymphocyte membrane are the target through which the alloantisera mediate specific immunosuppression