Immunosuppressive factor(s) specific for L-glutamic acid(50)-L- tyrosine(50) (GT). II. Presence of I-J determinants on the GT-suppressive factor

Abstract

The responses to the synthetic antigens, L-glutamic acid(60)-L- alanine(30)-L-tyrosine(10) (GAT) and L-glutamic acid(50)-L-tyrosine(50) (GT) are controlled by genes in the I region of the mouse H-2 complex (1-3). Preimmunization of the mice bearing the H-2(p,q,s) nonresponder haplotypes with GAT stimulates the development of suppressor T cells that inhibit in vivo or in vitro antibody responses to GAT complexed to the immunogenic carrier, methylated bovine serum albumin (GAT-MBSA) (4). The copolymer GT is not immunogenic in any inbred mouse strain tested, and has a suppressive effect on the antibody responses to GT-MBSA in mouse strains bearing the H-2(d,f,k,s) haplotypes; suppressor T cells have been demonstrated to be responsible for specific GT suppression (3). We have obtained specific suppressive extracts from thymus and spleen cells of GAT-or GT-primed suppressor strains (5,6). The specific suppressive T-cell factors in the active extracts have been characterized (6,7) and appear similar to the carrier-specific suppressor factor described by Tada and Taniguchi (8). These products belong to a family of newly identified molecules coded for by the I region of the H-2 complex with affinity for antigen and helper (9,10) or suppressive (5-8) regulatory activity on the immune response. Recently, Tada et al. have reported that the keyhole limpet hemocyanin (KLH)-specific suppressor factor is coded for by the I-J subregion of the H-2 complex (11). We now demonstrate also that a GT-specific suppressor factor extracted from the spleens and thymuses of B10.BR (H-2(k)) mice bears determinants controlled by the I-J subregion of the H-2 complex.

Reduction of syngeneic tumor growth by an anti-I-J-alloantiserum.

“…The identification of distinctive alloantigens on mouse suppressor T cells (9) and suppressor factors (8,10,11) strongly suggests that distinctive antigens also exist on human suppressor T cells and suppressor factor. The considerable antisuppressive activity of anti-I-J serum in the mouse raises the expectation that an antiserum specific for the human counterpart of the mouse I-J determinants could have useful therapeutic properties.…”

“…This tumor-specific suppressor T cell factor and other specific T cell factors capable of suppressing antibody responses (4)(5)(6) or contact sensitivity (7,8) have similar biological and immunochemical properties. Suppressor T cells (9) and specific suppressor factors (8,10,11) bear determinants coded for by the I-J subregion of the H-2 complex not displayed on other T cells or other immunological regulatory factors.…”

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

“…Interestingly, SF produced in A/J mice bear in addition to a genetically coded idiotypic determinant (14), a determinant encoded by genes in the K end of the H-2 MHC. In keeping with the nature of SF in a variety of systems (5)(6)(7)(8)22) it is probable that this determinant is controlled by the I-J subregion; studies are in progress to clarify this point.…”

“…These SF have in common a number of biochemical characteristics which allow comparisons within this family of biologically active molecules. SF in many cases bear antigen-specific recognition units (5,7,8,19,20), are proteins derived from the suppressor T cell (5, 9), bear determinants encoded by the I-J subregion of the H-2 MHC (5,6,8,22), and do not bear conventional determinants present on Ig light or heavy chains constant regions (5,7,19). The potential mechanisms by which SF manifests suppression include the stimulation and generation of second-order suppressor T cells in as yet an incompletely understood manner (23,24) and/or alternatively, the direct inactivation of T helper (23) or T-effector cells (20).…”

T cell receptors with allo-major histocompatibility complex specificity from rat and mouse. Similarity of size, plasmin susceptibility, and localization of antigen-binding region.

“…However, precise data on the structure of the T cell receptor are not abundant. Several different types of molecules have been described, thought to represent either antigen-specific T cell receptor molecules or molecules that communicate within the subsets o~" the immune cell orchestra (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Primary characteristics of all molecules described so far include the lack of conventional immunoglobulin Cn, VL, or CL determinants, and the presence of VH determinants (mainly idiotypes) within a heavy chain.…”