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) α and β chains, as well as their trimolecular complexes with peptide—MHC ligand, have established their structural similarity with the immunoglobulin molucules. The complementarity-determining region (CDR1) and CDR2 encoded within the TCR germline variable (V) sequence genes are well conserved across different TCR Vα and Vβ subfamilies. Muliple 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 coservation of a positive net charge in Vα subfamilies. A model has been proposed for a direct interaction of the lateral part of CDR2α with the negatively charged membrane-proximal ‘stalk’ region of the CD8 molecule.