Genetic Control of Sulbenicillin (SBPC)‐Induced T Cell Proliferation in Mice

Abstract

The major histocompatibility complex (MHC) control of T cell‐mediated response to drug‐derived determinants is not well understood. As a first step in studying the MHC control of drug hypersensitivity, semisynthetic penicillin, sulbenicillin (SBPC), was used as an antigen to establish an in vitro proliferative assay for mouse T cell response to this drug. The lymph node cells taken 7–9 days after immunization with 10 mg SBPC in complete adjuvant were tested for SBPC‐specific response in a standard 3 day proliferation assay. SBPC‐induced proliferation of the primed lymph node cells was mediated by the Thy‐1+, Lyt‐1+2– cells, i.e., helper type T (Th) cells. The Lyt‐1+2–, T cell proliferative responsiveness to SBPC was mapped on the I‐A locus within the H‐2 MHC regions. The proliferation was inhibited by the monoclonal antibody against Aβ molecules, product of the I‐A locus, but not by the monoclonal antibody against Eα molecules, product of the I‐E locus. These results indicate that the SBPC response of Lyt‐1+2–, Th cells is controlled by the I‐A locus, the products of which, the MHC class II A (AβAα) molecules, function as restriction molecules in the Th cell recognition of SBPC. The removal of the Lyt‐2+ suppressor type T (Ts) subset from the SBPC nonresponder cultures by a positive Lyt‐separation did not reverse the I‐A allele‐related nonresponsiveness. This result suggests that the nonresponsiveness is not due to the presence of the Lyt‐2+ Ts subset, but rather to the absence of the Lyt‐1+ Th subset, which recognizes SBPC together with self A molecules on the antigen presenting cell and proliferates in the SBPC nonresponder cultures.

Supplement of Exogenous IL2 Abrogates Induction of Tolerance in Drug‐Induced T Cell Proliferation

“…The cells were incubated with a I :20 dilution of Lyt-2.I-specific monoclonal antibody (Cedarlane LTD., Canada) at 4°C for I h, washed with the culture medium, and reincubated on goat anti-mouse immunoglobulin antibody (Cappel Lab. Inc., USA)-coated plastic dishes at 4°C for I h as described previously (5,6). The Lyt-I +2-subset was obtained from the nonadherent cell fraction and the Lyt-2 + subset from the adherent cell fraction prepared by rubbing with the end of a rubber policeman.…”