Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor

Using NMR spectroscopy, we determined the solution structure of a single-chain T-cell receptor (scTCR) derived from the major histocompatibility complex (MHC) class II-restricted D10 TCR. The conformations of complementarity-determining regions (CDRs) 3β and 1α and surface properties of 2α are different from those of related class I-restricted TCRs. We infer a conserved orientation for TCR V α domains in complexes with both class I and II MHC–peptide ligands, which implies that small structural variations in V α confer MHC class preference. High mobility of CDR3 residues relative to other CDR or framework residues (picosecond time scale) provides insight into immune recognition and selection mechanisms.