Conserved motifs in T-cell receptor CDR1 and CDR2: implications for ligand and CD8 co-receptor binding

Recent X-ray crystallographic structures of the T-cell receptor (TCR) alpha and beta chains, as well as their trimolecular complexes with peptide-MHC ligand, have established their structural similarity with the immunoglobulin molecules. The complementarity-determining region (CDR1) and CDR2 encoded within the TCR germline variable (V) sequence genes are well conserved across different TCR V alpha and V beta subfamilies. Multiple sequence alignments have been made based on structural information; they indicate that there will be only a limited number of canonical conformations for the first and second CDR loops. The limited diversity shown by CDRs 1 and 2 contrasts with the extreme junctional CDR3 diversity. Furthermore, CDR2 alignments have revealed conservation 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 with the negatively charged membrane-proximal 'stalk' region of the CD8 molecule.