Immunosuppressive factor(s) specific for L‐glutamic acid⁵⁰‐L‐tyrosine⁵⁰ IV. In vitro activity and immunochemical properties

Abstract

The responsiveness of BALB/c spleen cells to the terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT), the copolymer of L-glutamic acid50-L-tyrosine50 (GT) and the corresponding complexes with methylated bovine serum albumin (MBSA) has been studied in vitro in a modified Mishell-Dutton culture system. Cultures of BALB/c spleen cells respond to GAT, GAT-MBSA and GT-MBSA over a wide dose range. Contrary to in vivo findings BALB/c spleen cell cultures respond to GT in vitro although in a much narrower dose range. Lymphoid extracts from GT-primed BALB/c or B10.BR mice (GT-TSF) specifically suppress the GT-MBSA response in vitro. This culture system has allowed us to further investigate immunochemical properties of both BALB/c and B10.BR GT-TSF-GT-TSF from both strains display affinity for GT-Sepharose and bear determinants encoded by the I region of the H-2 complex. Moreover, we demonstrate that the suppressive activity from B10.BR mice is a molecule or a molecular complex which displays affinity for GT and bears determinants of the I-J subregion of the H-2k haplotype.

Presence of interchain disulfide bonds between two gene products that compose the secreted form of an antigen-specific suppressor factor.

“…In any event, the KLH-TsF reported in this paper resembles other antigen-specific T cell factors with suppressor function reported by Theze et al (2), and Kontiainen et al (5), and with helper function as described by Taussig et al (16), Isac et al (17), and Tokuhisa et al (18). In particular, the antigen-specific helper T cell factors have also demonstrated that they have the antigen-binding moiety and the I-A-encoded determinants.…”

Helper and suppressor T cell factors

“…Very recently, the ability of GAT-Ts to suppress nonresponder T cell proliferative responses to GAT after GAT-MBSA priming has also been used for studying suppression in this model [66]. The work ofTada et al [131] led to attempts to produce GAT and GT-TsF by sonication of spleen and thymus cells containing active T s. Such extracts did suppress GAT-MBSA or GT-MBSA responses of syngeneic mice, and were also active in vitro, permitting easy assay [69,70,147,150]. This antigen does not lead to responses in any tested inbred mouse strain, although it is immunogenic in an outbred line.…”

When All is said and Done

“…The genes controlling the development of GT-specifi c suppressor T cells mapped in the I region and behaved as complementing genes in both the cis and trans confi guration (73). As in the case of GAT-specifi c suppressors, lysis of GT-suppressor T cells yielded a GT-specifi c factor capable of suppressing GT-MBSA responses (74). In more recent experiments with this system, Vidovic et al investigated the ability of GT to initiate T cell proliferative responses rather than antibody production in inbred strains of mice; they observed that some of the suppressor haplotypes we had identified, i.e.…”