An antigen-specific helper T cell hybridoma produces an antigen-specific suppressor inducer molecule with identical antigenic fine specificity. Implications for the antigen recognition and function of helper and suppressor inducer T cells.

Abstract

We have previously described a T cell hybridoma, A.1.1, that responds to specific Ag (P18, a synthetic polypeptide of defined sequence) in the context of I-Ad by producing lymphokines. Herein we report that this cell also releases, into culture supernatants and ascites fluid, an Ag-specific activity that functions in the induction of suppression of anti-SRBC PFC responses. This suppressive activity requires a) Ag-non-specific accessory molecules from a T suppressor inducer factor, b) Ly-2+ T cells in the assay cultures, and c) the specific Ag (P18) conjugated to the SRBC in the assay cultures. The specificity of the A.1.1-derived activity was demonstrated by the absence of suppression in cultures containing SRBC, BSA-SRBC, or conalbumin-SRBC rather than P18-SRBC. Further, the A.1.1-derived activity bound to, and could be eluted from, P18 but not conalbumin. Using a panel of synthetic variant peptides, we have mapped the critical residues in P18 required for Ag/I-Ad induced activation of A.1.1. These peptides were tested for their ability to act as targets for the A.1.1-derived suppressive activity when conjugated to SRBC and added to assay cultures. All peptides capable of stimulating the A.1.1 T cells to release lymphokines were similarly effective in the suppressor assay. Thus, the recognition of Ag by the T cells and by the T cell-derived activity appeared to be identical. The A.1.1-derived molecule was found to be capable of inducing L3T4- T cells to act as suppressor T cells following culture. These suppressor cells were active in inhibiting anti-SRBC responses in the absence of P18 and bore the Ly-2 surface marker. Thus, it is likely that the function of this Ag-specific molecule is to induce Ly-2+ suppressor T cells and thereby cause the inhibition of the response. This function is distinct from that normally associated with helper T cells and may shed new light on the possible relationship between the cell surface T cell receptor for Ag and Ag-specific T suppressor inducer molecules.