Mapping of SJL/J reticulum cell sarcoma tumor-associated Ia antigens by T cell hybridomas: characterization of tumor-specific and shared epitopes detected on IE+ allogeneic cells

Abstract

Previous studies have suggested that reticulum cell sarcoma (RCS) tumor cells of SJL/J (IA + IE-) mice express neospecificities that are related to antigenic specificities characteristic of IE+ allogeneic cells. These neospecificities have also been suggested to play a role in the strong syngeneic antitumor proliferative response as well as in regulating RCS growth in vivo. The present studies characterize four RCS tumor-specific T cell hybridoma clones prepared from the fusion of BW5147 thymoma with T cells derived from lymph nodes of tumor-bearing mice. Upon stimulation, these hybridomas secrete IL 2 in the supernatant. Two hybridomas responded to RCS to IE+k and to IE+d allogeneic cells, respectively, and the other two hybridomas were tumor specific. The specificity of these hybridomas was assessed by response to both spontaneous and transplantable RCS lines and failure to stimulate a response by either normal or LPS-induced B cell blasts from the host SJL/J cells. The epitopes recognized by the T cell hybridomas were examined by the ability of several monoclonal antibodies to inhibit the IL 2-induced response by the T cell hybridomas. Antibodies directed against the IABs polypeptide of the IA hybrid molecule blocked the antitumor response by all four hybridomas. However, the response to allogeneic IE+ cells was not blocked by anti-IAs antibody but was blocked by antibodies directed against either the IAk,d or IEk,d hybrid molecules or the corresponding alpha- or beta-chains. The response to both RCS and allogeneic cells was blocked by monoclonal antibodies directed against L3T4 antigens on the T cells. Based on the exquisite specificity of the T cell receptors, the results here demonstrate that RCS tumor cells express on their surface both tumor-specific I-A-associated epitopes and Ia-associated antigenic specificities that are shared with IE+ allogeneic cells. The present studies of adapting T cell hybridomas and blocking antibodies proved useful to characterize and map distinct tumor-associated epitopes on the surface of tumor cells. These findings, when combined with structural studies, should help unravel the molecular complexity of tumor-associated antigens.