Inhibition of dual Ir gene-controlled T-lymphocyte proliferative response to poly (Glu56Lys35Phe9)n with anti-Ia antisera directed against products of either I-A or I-C subregion.

Abstract

Previous studies have demonstrated that both the antibody and T-lymphocyte proliferative immune responses to poly(Glu3Lys36Phe") (GL$) are under the control of two major histocompatibility-linked immune response (Ir) genes. One gene, termed lIrGLt-a, has been mappe to the IC or I-E subregion of the major histocompatibility complex, while the other, termed Ir-GL$-ft, has been mapped to the I-A subregion.In this paper we examine the effect of anti-I-region-associated (Ia) antisera on the T4ymphocyte proliferative response to GL$. Antibodies directed against Ia antigens coded for by genes in either the I-A or IC subregion were found to inhibit the proliferative response to GLU. These results suggest that a function mediated by two Ir gene products can be blocked by anti-Ia antisera directed against either one, and thus, that both products are expressed on the cell surface. We have previously demonstrated that in vitro antigen-induced proliferative responses of thymus-derived (T) lymphocytes can be inhibited by anti-Ia antisera (1). When the response being studied was under the control of specific immune response (Ir) genes, the anti-Ia inhibition showed haplotype specificity; that is, the proliferative response of T lymphocytes from primed (responder X nonresponder) F1 hybrids could only be blocked by antisera directed against Ia antigens coded for by the major histocompatibility complex (MHC) alleles of the responder parent. Furthermore, in instances in which an Ir gene had been mapped to a particular subregion of I, anti-Ia antisera specific for products of that subregion could inhibit activation. These results suggested an intimate relationship at the cell surface (or possibly in the culture supernatant) between Ia antigens and the molecules that mediate Ir gene function.We have also demonstrated that the immune response to poly(Glu53Lys36Phe11)n (GL4) is under the control of two MHC-linked Ir genes (2, 3). This requirement holds for both antibody formation (2) and T-lymphocyte proliferation (3). One gene, termed Ir-GL 4-a, was mapped to the I-C or I-E subregion of the MHC, and the other gene, termed Ir-GL4l-3, was mapped to the I-A subregion (4). In order to assess the relative functions of both gene products and, in particular, to ascertain whether both products had to function on the cell surface for activation to occur, it was of interest to determine the effect of anti-Ia antisera on the GL4-induced proliferative response.Because the two genes controlling the GLUE response are located in different subregions of the MHC, it was possible to selectively test the inhibitory effect of anti-Ia antisera directed against the products of each subregion. The experiments presented in this MATERIALS AND METHODS Animals. BALB/cAnN mice were obtained from the Division of Research Services, National Institutes of Health.B1O.D2/nSn, C57BL/lOSn (B10), A/J, and BlO.A(5R)/SgSn mice were purchased from the Jackson Laboratory, Bar Harbor, ME. The recombinant strains A.TH/SF, A.TL/SF, B1O.HTT/SF, BIO.S(9R)/Sg, D2.GD, an...

Mechanism responsible for the induction of I-J restriction on TS3 suppressor cells.

“…Thus, genes in the I-A and I-E subregions control helper T cell induction, whereas genes in the I-J subregion control Ts3 induction. The functional role of I-A or I-E gene products in the presentation of antigen by macrophages or dendritic cells has been well documented (34,36). We hypothesize that I-J-encoded structures on antigen-presenting cells can serve a similar presentation function.…”

Complementation of H-2-linked genes controlling immune responsiveness

“…Schwartz et al [76] demonstrated that the proliferative response to GL~ could be blocked with anti-Ia sera specific for products of either of the I subregions which encode for the Ir-GL~ genes. Thus, the responses of B10.HTT and 9R T lymphocytes could be blocked by antisera directed against the I-E, I-C subregions (Table 16).…”

Antigen-presenting cell function in induction of helper T cells for cytotoxic T-lymphocyte responses: evidence for antigen processing.

“…Macrophages are required for the uptake and presentation of soluble protein antigens that precedes in vitro T-lymphocyte proliferation and T-and B-lymphocyte collaboration for an antibody response. Further, macrophage-lymphocyte interactions are regulated by the major histocompatibility complex (8)(9)(10)(11), specifically, by the Ia molecules on the sensitizing macrophages (12)(13)(14). Macrophage uptake and presentation is not limited to soluble protein antigens; it has recently been shown that radio-resistant splenic adherent cells (SACs) are required for the generation of cytotoxic T-lymphocyte (CTL) responses to both allogeneic membrane proteins (7) and trinitrophenyl-modified cells (6).…”