Antigen-specific T-cell factor in cell cooperation. Mapping within the I region of the H-2 complex and ability to cooperate across allogeneic barriers.

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.

Section: Discussionmentioning

confidence: 85%

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

Thèze

Waltenbaugh

Dorf

et al. 1977

“…cluding helper T-cell-replacing factors (17,18) and suppressor factors (19,20). These molecules share certain properties: mol wt of approximately 50,000, antigen-binding sites, the lack of Ig determinants, and the presence of determinants recognized by alloantisera specific for I-region gene products.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) II. Cellular source and effect on responder and nonresponder mice.

Kapp¹,

Pierce²,

Benacerraf³

1977

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder strains of mice, but does stimulate the development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT antibody responses to GAT complexed to methylated bovine serum albumin (GAT-MBSA). Furthermore, extracts prepared from lymphoid cells of GAT-primed, but not control, nonresponder mice inhibit the development of antibody responses to GAT-MBSA by normal nonresponder mice. This suppression is specific, dose-dependent, and can be readily analyzed in vitro. The suppressive factor is a T-cell product. An extract from GAT-primed DBA/1 mice inhibits the response to GAT-MBSA by spleen cells from histoincompatible strains of mice that are nonresponders to GAT, but not strains that are responders to GAT.

“…Whether the supernate of alloantigen-activated cells contains Ia moieties is not presently known. However, complex molecules containing such/-region products have been identified in other T-cell factors which mediate regulatory cell interactions in antibody synthesis (12)(13)(14). Although MLR responder cells have been reported to lack Ia antigen (7), it is possible that such molecules are exposed or altered to a definable configuration subsequent to antigen stimulation, providing the appropriate site of interaction with an Ia-containing suppressor factor.…”

Section: Mlrmentioning

confidence: 99%

Regulatory mechanisms in cell-mediated immune responses. III. I-region control of suppressor cell interaction with responder cells in mixed lymphocyte reactions.

Rich¹,

Rich²

1976

Active suppression of mixed lymphocyte reaction (MLR) response is mediated by a soluble factor released by alloantigen-activated murine suppressor cells. Genetic restrictions controlling suppressor factor interaction with MLR responder cells were elucidated in this study. Non-H-2 genetic background was irrelevant to effective interaction. Using congenic strains and strains with intra-H-2 recombinants the genetic locus controlling suppressor T-cell-responder cell interaction was mapped in the I-C or S regions of the H-2 complex. Similarly, recombinant strains were used to exclude the presence of another suppressor cell-responder cell interaction locus in K,I-A, and I-B regions. It thus appears that the I-C subregion of the H-2 complex controls suppressive cell interactions in this T-cell-mediated immune response.