Efficient discovery of immune response targets by cyclical refinement of QSAR models of peptide binding

J Mol Graph Model. 2001;19(5):405-11, 467. doi: 10.1016/s1093-3263(00)00099-1.

Abstract

Peptides that induce and recall T-cell responses are called T-cell epitopes. T-cell epitopes may be useful in a subunit vaccine against malaria. Computer models that simulate peptide binding to MHC are useful for selecting candidate T-cell epitopes since they minimize the number of experiments required for their identification. We applied a combination of computational and immunological strategies to select candidate T-cell epitopes. A total of 86 experimental binding assays were performed in three rounds of identification of HLA-A11 binding peptides from the six preerythrocytic malaria antigens. Thirty-six peptides were experimentally confirmed as binders. We show that the cyclical refinement of the ANN models results in a significant improvement of the efficiency of identifying potential T-cell epitopes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Protozoan / immunology*
  • Computer Simulation*
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A Antigens / immunology*
  • HLA-A11 Antigen
  • Humans
  • Neural Networks, Computer*
  • Peptides / chemical synthesis
  • Peptides / immunology*
  • Plasmodium falciparum / immunology*
  • Protein Binding

Substances

  • Antigens, Protozoan
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A11 Antigen
  • Peptides