ANTIGEN-SPECIFIC THYMUS CELL FACTORS IN THE GENETIC CONTROL OF THE IMMUNE RESPONSE TO POLY-(TYROSYL, GLUTAMYL)-POLY-D, L-ALANYL--POLY-LYSYL

Abstract

The genetic control of the antibody response to a synthetic polypeptide antigen designated poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(T, G)-A--L] has been studied in congenic high responder C3H.SW (H-2b) and low responder C3H/HeJ (H-2k) strains of mice. This response is controlled by the Ir-1 gene and is H-2 linked. The method employed was to study the ability of specifically primed or "educated" T cells of each strain to produce cooperative factors for (T, G)-A--L in vitro. Such factors have been shown to be capable of replacing the requirement for T cells in the thymus-dependent antibody response to (T, G)-A--L in vivo. The T-cell factors produced were tested for their ability to cooperate with B cells of either high or low responder origin by transfer together with bone marrow cells and (T, G)-A--L into heavily irradiated, syngeneic (for bone marrow donor) recipients. Direct anti-(T, G)-A--L plaque-forming cells were measured later in the spleens of the recipients. The results showed that (a) educated T cells of both high and low responder origin produced active cooperative factors to (T, G)-A--L, and no differences between the strains in respect to production of T-cell factors could be demonstrated; and (b) such factors, whether of high or low responder origin, cooperated efficiently with B cells of high responder origin only, and hardly at all with B cells of low responder origin. The conclusion was drawn that the cellular difference between the two strains lies in the responsiveness of their B cells to specific signals or stimuli received from T cells. As far as could be discerned by the methods used, no T-cell defect existed in low responder mice and the expression of the controlling Ir-1 gene was solely at the level of the B cells in this case.

Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization.

“…The immunochemical and physicochemical properties of the suppressive Tcell factor are much like those of the antigen-specific cooperative T-cell factor reported by Taussig and his associates (22,(31)(32)(33), although the effect is quite opposite . Their factor is released from educated T cells by a short-term culture with antigen, and cooperates with bone marrow cells to induce antibody response to the same antigen in irradiated hosts.…”

“…Their factor is released from educated T cells by a short-term culture with antigen, and cooperates with bone marrow cells to induce antibody response to the same antigen in irradiated hosts. Although their factor could cooperate with H-2 histoincompatible bone marrow cells (32), the factor contains antigen coded for by genes in the left-hand side of the H-2 complex (33) . It has specificity and affinity for the immunizing antigen, but is not an Ig in nature (22,31) .…”

Bifunctional major histocompatibility-linked genetic regulation of cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes.

“…The expression of the genetic defect at the level of cell-to-cell interaction could be analogous to that suggested for the mechanism of action of Ir genes controlling antibody production to thymusdependent antigens (16,17). A distinction between these two alternatives has not yet been realized .…”

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.

“…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.…”