Crystal structures of T cell receptor β chains related to rheumatoid arthritis

The crystal structures of the Vβ17+ β chains of two human T cell receptors (TCRs), originally derived from the synovial fluid (SF4) and tissue (C5–1) of a patient with rheumatoid arthritis (RA), have been determined in native (SF4) and mutant (C5–1F104→Y/C187→S) forms, respectively. These TCR β chains form homo-dimers in solution and in crystals. Structural comparison reveals that the main-chain conformations in the CDR regions of the C5–1 and SF4 Vβ17 closely resemble those of a Vβ17 JM22 in a bound form; however, the CDR3 region shows different conformations among these three Vβ17 structures. At the side-chain level, conformational differences were observed at the CDR2 regions between our two ligand-free forms and the bound JM22 form. Other significant differences were observed at the Vβ regions 8–12, 40–44, and 82–88 between C5–1/SF4 and JM22 Vβ17, implying that there is considerable variability in the structures of very similar β chains. Structural alignments also reveal a considerable variation in the Vβ–Cβ associations, and this may affect ligand recognition. The crystal structures also provide insights into the structure basis of T cell recognition of Mycoplasma arthritidis mitogen (MAM), a superantigen that may be implicated in the development of human RA. Structural comparisons of the Vβ domains of known TCR structures indicate that there are significant similarities among Vβ regions that are MAM-reactive, whereas there appear to be significant structural differences among those Vβ regions that lack MAM-reactivity. It further reveals that CDR2 and framework region (FR) 3 are likely to account for the binding of TCR to MAM.