Genetic Control of Immune Responses in Vitro

Abstract

Although nonresponder, H-2s and H-2q, mice fail to develop GAT-specific PFC responses to GAT, they do develop GAT-specific PFC responses when stimulated by GAT complexed to an immunogenic carrier such as methylated bovine serum albumin. The studies described in this paper show that injection of nonresponder mice with GAT specifically decreases their ability to develop anti-GAT PFC responses to a subsequent challenge with GAT-MBSA. Addition of GAT to cultures of spleen cells from nonresponder mice also prevents development of the GAT-specific PFC responses stimulated by GAT-MBSA. Thus, interaction of nonresponder spleen cells with GAT leads to the induction of unresponsiveness in vivo and in vitro. Various parameters of the tolerance induction have been investigated and described. A comparison of the effects of GAT on B cells indicates that nonresponder B cells are more readily rendered unresponsive by soluble GAT than are responder B cells. The significance of these data for our understanding of Ir gene regulation of the immune response is discussed.

Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).

“…In contrast, the F, crosses between GAT responders and nonresponders behaved as responders to GAT, in keeping with the dominant character of H-2-linked Ir genes, indicating that responder phenotypes are dominant over suppressor phenotypes (2,3). The other major conclusion from the strain distribution of GT-induced suppression ofGT-MBSA responses is that the Is gene(s) controlling these responses are coded for in the H-2 complex.…”

“…To determine if suppression induced by GT is distinct from that induced by GAT, we compared the effect of immunization with GT and GAT in DBAA (H-29) and SJL (H2$) mice on the PFC responses to these copolymers complexed with MBSA. These strains were selected for the experiments because GAT stimulates GAT-specific T cells capable of suppressing GAT-MBSA PFC responses in both strains (3,5), whereas GT is able to suppress GT-MBSA responses in SJL, but not in DBA/1 mice.…”

“…Selected noaresponder strains of mice, DBA/1 (H2Q) and SJL (H-2s), were injected intraperitoneally with 10 lAg or 100 Wg of GAT as GAT-MBSA in a mixture of Maalox and pertussis vaccine (Eli Lilly & Co ., Indianapolis, Ind .) as previously described (3) .…”

Restriction of primary responses to the IgG class and dependency of IgM responses on secondary immunization for the copolymers of L-glutamic acid, L-tyrosine, and L-alanine.

“…Earlier studies from our laboratory have shown that injection of GT or GAT into nonresponder mice bearing the H-2 d or H-2 q haplotype stimulate suppressor T cells capable of inhibiting antigen-specific IgG PFC responses to GT-MBSA or GAT-MBSA, respectively (5,12). The effect of GT preimmunization on the IgM and IgG PFC responses of BALB/c mice is shown in Table VI.…”

“…Previous studies from our laboratory demonstrated that immunization of nonresponder mice with GAT or GT stimulates the development of specific T cells capable of suppressing the primary IgG responses to GAT-MBSA (12) and GT-MBSA, respectively (5). The ability to elicit secondary IgM responses to these antigens permitted us to verify that such responses are also suppressed in nonresponder animals by preimmunization with the uncomplexed copolymers.…”