Structural Motifs in Rheumatoid T-Cell Receptors

The linkage of rheumatoid arthritis (RA) to HLA-DR haplotypes, high levels of HLA-DR expression, and T-cell infiltration in the joints, indicate a central role for the interaction of T-cell receptors (TCR) with antigen (Ag) + major histocompatibility complex (MHC) complexes in pathogenesis. Receptor analysis in RA has uncovered a restricted heterogeneity of TCR transcripts, suggesting an antigen-driven response. We analyzed the sequence and structural features of RA-associated TCRs in light of the recently published TCR crystal structures. The surface-exposed residues of the third complementarity-determining region (CDR3s) showed preferential use of certain amino acid residues when sequences derived from synovial fluid or tissue were compared with those derived from peripheral blood, particularly for α chains. Sequence alignment of oligoclonal synovial TCR CDR3s revealed groupings with similar CDR3 lengths and amino acid compositions, which suggests shared antigen recognition. Given the limitations of ana...