Biased amino acid distributions in regions of the T cell receptors and MHC molecules potentially involved in their association.
We have analysed, in the context of the available structural information, the frequency of occurrence of different amino acids in functional regions of both the class I MHC antigens and of the TCR alpha and beta chains. We found that in class I MHC molecules, charged residues are found frequently among those which are presumably dedicated to interactions with the TCR, while the aromatic side chain residues are found more in the interior of the groove. In the TCR, the Asn residue appears with high frequency in all the CDR equivalents. The TCR CDR3s of both alpha and beta chains are particularly rich in Gly, whereas the CDR1 and CDR2 loops exhibit strong biases in favour of charged residues. Accordingly, the interactions between the MHC molecule and the peptide antigen appear to be essentially mediated by hydrophobic interactions and hydrogen bonding, while electrostatic interactions between charged residues might be important in the association of TCR and MHC molecules. The observation that each CDR1 and CDR2 is biased towards a particular set of amino acids, taken together with the nature of the protruding residues on the MHC helices, allows us to propose, in the frame of a molecular model of the MHC-TCR complex, several plausible configurations.
Unité d'Informatique Scientifique, Gène INSERM U277, Institut Pasteur, Paris, France.
A
A
Prochnicka-Chalufour
J L
JL
Casanova
S
S
Avrameas
J M
JM
Claverie
P
P
Kourilsky
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D004560:Electricity; D005805:Genes, MHC Class I / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology; D016415:Sequence Alignment
D000596:Amino Acids; D011948:Receptors, Antigen, T-Cell