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.
Arden
B
B
Immunbiologie, Augenklinik, Klinikum Innenstadt, München, Germany. arden@embl-heidelberg.de
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D017124:Conserved Sequence; D006801:Humans; D008024:Ligands; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta
D016827:CD8 Antigens; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019158:N-Acetylneuraminic Acid