CONSERVED MOTIFS IN T-CELL RECEPTOR CDR1 AND CDR2 - IMPLICATIONS FOR LIGAND AND CD8 CORECEPTOR BINDING

Recent X-ray crystallographic structures of the T-cell receptor (TCR) alpha and beta chains, as well as their trimolecular complexes with pe ptide-MHC ligand, have established their structural similarity with th e immunoglobulin molecules. The complementarity-determining region (CD R1) and CDR2 encoded within the TCR germline variable (V) sequence gen es are well conserved across different TCR V alpha and V beta subfamil ies. Multiple sequence alignments have been made based on structural i nformation; they indicate that there will be only a limited number of canonical conformations for the first and second CDR loops. The limite d diversity shown by CDRs 1 and 2 contrasts with the extreme junctiona l CDR3 diversity. Furthermore, CDR2 alignments have revealed conservat ion of a positive net charge in V alpha subfamilies. A model has been proposed for a direct interaction of the lateral part of CDR2 alpha wi th the negatively charged membrane-proximal 'stalk' region of the CD8 molecule.