Modeling the peptide-T cell receptor interaction by the comparative molecular similarity indices analysis-soft independent modeling of class analogy technique.
A set of 38 epitopes and 183 non-epitopes, which bind to alleles of the HLA-A3 supertype, was subjected to a combination of comparative molecular similarity indices analysis (CoMSIA) and soft independent modeling of class analogy (SIMCA). During the process of T cell recognition, T cell receptors (TCR) interact with the central section of the bound nonamer peptide; thus only positions 4-8 were considered in the study. The derived model distinguished 82% of the epitopes and 73% of the non-epitopes after cross-validation in five groups. The overall preference from the model is for polar amino acids with high electron density and the ability to form hydrogen bonds. These so-called "aggressive" amino acids are flanked by small-sized residues, which enable such residues to protrude from the binding cleft and take an active role in TCR-mediated T cell recognition. Combinations of "aggressive" and "passive" amino acids in the middle part of epitopes constitute a putative TCR binding motif.
Doytchinova
Irini A
IA
The Jenner Institute, University of Oxford, Compton, Berkshire RG20 7NN, United Kingdom.
Flower
Darren R
DR
D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry; D018360:Crystallography, X-Ray; D000939:Epitopes; D015791:HLA-A3 Antigen / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry*; D055672:Static Electricity
D000596:Amino Acids; D000939:Epitopes; D015791:HLA-A3 Antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell