Characterization of a T-cell clone recognizing idiotypes as tumor-associated antigens

Although heterogeneous T cells recognizing idiotypic determinants have been demonstrated to occur spontaneously in vitro or to be expanded by immunization with antigen or idiotype, their in vitro propagation and cloning was not successful. These previous studies have relied extensively on soluble immunoglobulin to induce proliferation of idiotype-specific T cells. This report describes a unique approach to obtain a stable T-cell clone specific for a monoclonal beta 2-6 fructosan binding myeloma ABPC48 (BALB/c origin), bearing well-defined A48 regulatory idiotopes. Following repeated immunizations with ABPC48 myeloma protein of C.B/R3 mice (H-2d, VHb, CHa), which differ only in the VH locus from BALB/c mice (H-2d, VHa CHa), several stable T-cell clones were obtained after stimulation in vitro with ABPC48 myeloma cells. The proliferation of a T-cell clone A48.B2 was observed with irradiated myeloma cells or hybridomas producing antibodies bearing A48 idiotype encoded by genes deriving from the VH 441-4 family. Proliferation of the clone did not occur with soluble ABPC48 myeloma protein or with Sepharose 4B-bound ABPC48 myeloma protein. Both anti-A48Id and anti-Iad monoclonal antibodies can specifically inhibit the proliferation of this clone when stimulated with ABPC48 myeloma cells. These results demonstrate recognition of idiotypes on B-cell tumours by T cells and implicate the role of class II major histocompatibility complex determinants in this cellular interaction.