T cell receptor beta-chain third complementarity-determining region gene usage is highly restricted among Sm-B autoantigen-specific human T cell clones derived from patients with connective tissue disease

Objective. To determine the structure of T cell receptors (TCR) used by Sm- B-reactive human T cell clones, to map T cell epitopes on the Sm-B autoanti gen, and to determine the HLA restriction element used in the recognition o f Sm-B by T cells. Methods. Sm-B-reactive T cell clones were generated from patients with conn ective tissue disease by using either a recombinant fusion protein or synth etic peptides. The TCR structure was defined with the use of polymerase cha in reaction and DNA sequencing. Synthetic peptides were used to map T cell epitopes on Sm-B. HLA restriction element usage was defined by using monocl onal antibody blocking. Results. Usage of the TCR third complementarity-determining region (CDR3) w as highly restricted among Sm-B autoantigen-specific human T cell clones. O nly amino acids 48-96 of the Sm-B2 autoantigen were recognized by T cells, and this occurred in the context of HLA-DR. Conclusion. TCR CDR3 gene usage is highly conserved by Sm-B autoantigen-spe cific T cell clones, and this appears to be related to the recognition of a limited number of T cell epitopes on the Sm-B autoantigen presented in the context of HLA-DR.