Generation and characterization of a clonotypic antibody specific for the T cell receptor of an arthritogenic T cell clone-studies in adjuvant arthritis

Adjuvant Arthritis (AA) can be induced by passive transfer of a T cell clon e (A2b) derived from arthritic rats, specific for Heat Shock Protein 60, HS P60 176-190. Furthermore, a crucial role for T cells with HSP60 176-190 spe cificity in AA was shown by induction of tolerance using HSP60 176-190 or b y immunization with an altered peptide ligand based on the same sequence. T o study clonal expansion of A2b-like T cells during AA and to determine the ir role in AA induction, we generated a clonotypic antibody, 16C4, specific for the TCR of the A2b T cell clone (TCR AV11S1/BV18). This antibody stain ed A2b T cells in flow cytometry experiments, induced proliferation of A2b cells when fixed on a solid support, and inhibited antigen-induced A2b prol iferation when added in solution. A2b-like T cells were detected in a low f requency in lymphoid organs of arthritic rats. Thus, as in ai ilo administr ation of 16C4 did not inhibit AA, cells containing the determinant recogniz ed by 16C4 are possibly not the sole contributors to AA development. Furthe rmore, epitope specific interventions by antigen administration may be poss ible even in cases where the epitope specific T cell clonotype is of low fr equency. (C) 2000 Academic Press.