An Alternative Conformation of the T-Cell Receptor α Constant Region

αβ T-cell receptors (TcRs) play a central role in cellular immune response. They are members of the Ig superfamily, with extracellular regions of the α and β chains each comprising a V-type domain and a C-type domain. We have determined the ectodomain structure of an αβ TcR, which recognizes the autoantigen myelin basic protein. The 2.0-Å-resolution structure reveals canonical main-chain conformations for the V(α), V(β), and C(β) domains, but the C(α) domain exhibits a main-chain conformation remarkably different from those previously reported for TcR crystal structures. The global IgC-like fold is maintained, but a piston-like rearrangement between BC and DE β-turns results in β-strand slippage. This substantial conformational change may represent a signaling intermediate. Our structure is the first example for the Ig fold of the increasingly recognized concept of “metamorphic proteins.”