Antigen-specific soluble helper molecules are produced during major histocompatibility complex-disparate allograft priming. Genetic mapping studies with appropriate recombinant and mutant lines of mice have defined the antigen specificities of the soluble helper molecules described here as being directed against the H-2D?d? molecules. The production of antigen-specific helper molecules is a relatively early event after H-2D?d? region allograft priming. Supernatants containing the antigen-specific helper molecules have no, or at least undetectable levels of, interleukin-2 (IL-2). Also, from the draining lymph nodes, we have demonstrated a later phase of factor production near the time of graft rejection that does contain nonspecific helper factors and IL-2. We have further demonstrated that supernatants obtained six days after allograft priming contain MHC-restricted factors that activate IL-2 production. In other studies we have demonstrated that monoclonal antibodies directed against the T-cell surface molecule, L3T4, block the generation of syngeneic cytolytic effectors against TNP-altered self. The mAb-mediated inhibition results in the induction of active suppressor cells. The induction of suppressors can be overcome by a mixture of recombinant IL-2 and a second T-cell-derived factor. A T-cell hybridoma has been isolated that produces this second """"""""helper factor."""""""" (LB) The T-cell hybridoma derived """"""""helper factor"""""""" contains no functional IL-2, IL-3, or gamma interferon. In another series of studies we have examined the mechanisms of genetic control to T cell responses to the MHC antigen, H-2D?b?. We have demonstrated that both responders and nonresponders produce IL-2; however, responders in addition make a second helper factor that is required for the differentiation of cytolytic T cells. Thus, the regulation of a positive response to D?b? appears to require helper cells that produce a distinct factor that is active in supporting the differentiation of CTL. (LB)
| Rangnekar, V M; Thomas, L S; Plate, J M (1988) Immunoprecipitation of interleukin-1 receptors from a mouse thymoma cell line, EL-4. J Biol Chem 263:16408-13 |
| Rangnekar, V M; Plate, J M (1988) Interleukin-1 receptor-like proteins synthesized by translation, in vitro, of immunopurified polysomal messenger RNA. J Biol Chem 263:16414-20 |
| Plate, J M; Lukaszewska, T L; Bustamante, G et al. (1988) Cytokines involved in the generation of cytolytic effector T lymphocytes. Ann N Y Acad Sci 532:149-57 |
