A Novel Predictive Technique for the MHC Class II Peptide-Binding Interaction
Antigenic peptide is presented to a T-cell receptor through the formation of a stable complex with a Major Histocompatibility Complex (MHC) molecule. Various predictive algorithms have been developed to estimate a peptide’s capacity to form a stable complex with a given MHC Class II allele, a technique integral to the strategy of vaccine design. These have previously incorporated such computational techniques as quantitative matrices and neural networks. We have developed a novel predictive technique that uses molecular modeling of predetermined crystal structures to estimate the stability of an MHC Class II peptide complex. This is the 1st structure-based technique, as previous methods have been based on binding data. ROC curves are used to quantify the accuracy of the molecular modeling technique. The novel predictive technique is found to be comparable with the best predictive software currently available.
MN Davies would like to thank the Biotechnology and Biological Sciences Research Council and the Anthony Nolan Research Institute for their financial support. The authors would also like to extend their thanks to Dr Andy Purkiss for his help in setting up the simulations and Dr Paul Travers for his advice on all things immunological.
- 8.Sturniolo T, Bono E, Ding J, Raddrizzani L, Tuereci O, Sahin U, Braxenthaler M, Gallazzi F, Protti MP, Sinigaglia F, Hammer J. (1999) Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices. Nat. Biotechnol. 17:555–61.CrossRefGoogle Scholar
- 14.Case DA et al. (1999) AMBER 6. San Francisco,CA, Univ. of California.Google Scholar
- 15.Pearlman DA, Case DA, Caldwell JW, Ross WS, Cheatham TE III, DeBolt S, Ferguson DM, Seibel GL, Kollman PA. (1995) AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comp. Physics Communic. 91:1–41.CrossRefGoogle Scholar