The I-J subregion codes for determinants on suppressor factor(s) which limit the contact sensitivity response to picryl chloride

Abstract

The cell-mediated immune reactivity (CMI) of mice to contact chemicals such as picryl chloride (PCI) is influenced by thymus-derived suppressor T lymphocytes (1,2). The development of these suppressor T lymphocytes is stimulated by the intravenous administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Zembala and Asherson have further demonstrated that a specific suppressor factor(s) can be detected in the supernates of cultured suppressor T cells. This factor suppresses the transfer of contact sensitivity (CS) to PCl (1,2). In experiments reported elsewhere (3), we have shown that the PCl suppressor supernates of Zembala and Asherson can also suppress the development of contact sensitivity to PCl. The immunochemical analysis of suppressor factor (SF) operative in the CS response to PCl has revealed many similar properties (3) to other suppressive moieties functioning to limit the plaque-forming cell (PFC) response to dinitrophenylated-keyhole limpet hemocyanin (DNP-KLH) as well as the strict antigen specificity of each respective suppressive factor, suggested that there might be a common origin of these substances. Indeed, in each case these respective factors were found to bear determinants controlled by the H-2 gene complex (4,5). Recently, in selected systems, the I-J subregion has been found to code for the Ia determinants present on suppressor cells (6) and suppressor factors (4,5). In accord with these findings, we report that antigen-specific SF which limit the CS response to PCl bear I-J determinants, implying that analogous suppressive regulatory mechanisms in CMI as well as antibody responses may be determined by genes of one subregion of the H-2 complex.

Mechanisms of regulation of cell-mediated immunity. III. The characterization of azobenzenearsonate-specific suppressor T-cell-derived-suppressor factors.

“…As can be seen in Fig. 2, the SF appears to be present in the fraction with mol wt 33-68,000, in agreement with previous results on the size of antigen-specific SF (3,8). It should be noted that some suppressive activity was also apparent in the smaller (<33,000) and the larger (>68,000) fractions.…”

“…The preparation of B10 anti-B10.A (anti-KkI-AkI-BkIJklC'tSdD a) and BI0.D2 anti-B10.A (anti-KkI-AkI-BkI-jkI-E k) was described previously (7,8). Briefly, sera were obtained after 6-10 biweekly ip.…”

“…Suppressor T cells in a variety of systems including that studied by Tada et al (3,5), Benacerraf and colleagues (4,16,19) and Greene et al (7,8), as well as Zembala and Asherson (20), elaborate specific subcellular moieties which can mediate suppression. These SF have in common a number of biochemical characteristics which allow comparisons within this family of biologically active molecules.…”

“…Thus, SF derived from STC induced by ABA conjugated ceils specifically limits ABA DTH reactivity. The specificity of TNBS induced SF has been reported elsewhere (8,20). with SF.…”

T cell surface I-J glycoprotein. Concerted action of chromosome-4 and -17 genes forms an epitope dependent on alpha-D-mannosyl residues.

“…However, I-J k expression is cell cycle dependent (19); nonsynchronous cells were used and I-J k molecule synthesis was not demonstrated at the time of mRNA extraction (28). Finally, E~ or E~ polypeptide molecular weights do not match reported I-J k polypeptide weights (40,(43)(44)(45)(46).…”