Extracellular (soluble) antigen-specific T cell proteins related to the T cell receptor for antigen (sTCRr): serologic and primary amino acid sequence similarity to T cell receptor alpha chains and association with cytokines

Abstract

Antigen-specific-effected immunoregulation by T lymphocytes is mediated by extracellular proteins produced by T lymphocytes. These immunoproteins bind specifically to nonprocessed antigen and either induce antigen-specific immunoregulatory T cells (tsfi) or effect regulation (tsfe). T cell proteins that bind specifically to nonprocessed antigen have ben termed "T cell antigen-binding molecules" (TABM), and by definition, tsfe and tsfi are, in part, TABM. To characterize tsfi, tsfe, and TABM and understand the relationships and function of these immunoproteins, we have combined the efforts of two laboratories to compare tsfi, tsfe, and TABM isolated by each laboratory. Data obtained in one laboratory were reproduced by the other, and all reagents prepared by each laboratory were exchanged. TABM, tsfi, and tsfe were found to express TCRCalpha epitopes but not TCRCbeta epitopes. The amino acid sequence of a tryptic peptide of a T cell hybridoma TABM specific for nitrophenylhydroxy acetate (NP) is similar to a TCRalpha chain and TCR pre-alpha chain amino acid sequence. ELISA and immunoblotting demonstrated that Mr 77,000 T cell hybrid-derived tsfi, tsfe, and TABM are noncovalently associated with Mr 15,000-16,000 interleukin-10 (IL-10). ELISA also demonstrated that tsfi and tsfe are associated with I-J. The ability of tsfi and tsfe to suppress a mixed lymphocyte reaction was prevented by anti-IL-10 or anti-I-J antibodies, suggesting that antigen-specific immunoregulatory T cell proteins function by an antigen-specific focusing of immunoregulatory cytokines.