Toward the quantitative prediction of T-cell epitopes: CoMFA and CoMSIA studies of peptides with affinity for the class I MHC molecule HLA-A*0201

A set of 102 peptides with affinity for the class I MHC HLA-A*0201 molecule was subjected to three-dimensional quantitative structure-affinity relatio nship (3D QSAR) studies using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). A test set of 50 peptides was used to determine the predictive value of the models. Th e CoMFA models gave q(2) and r(2)pred below 0.5. The best CoMSIA model has q(2) = 0.542 and r(2)pred = 0.679, and includes hydrophobic, steric, and H- bond donor fields. The hydrophobic interactions play a dominant role in pep tide-MHC molecule binding. CoMSIA coefficient contour maps were used to ana lyze the structural features of the peptides accounting for the affinity in terms of the three positively contributing physicochemical properties: loc al hydrophobicity, steric bulk and hydrogen-bond-donor ability.