An HLA-binding-motif-aided Peptide Epitope Library: A Novel Library Design for the Screening of HLA-DR4-restricted Antigenic Peptides Recognized by CD4+T Cells

J Hum Genet. 1998;43(1):14-21. doi: 10.1007/s100380050031.

Abstract

Susceptibility to a series of autoimmune diseases is strongly associated with particular HLA class II alleles. Identification of T cell clones and antigenic epitopes bound by HLA class II molecules involved in autoimmune diseases is critical to understanding the etiology of these HLA class II-associated diseases. However, establishment of T cell clones in autoimmune diseases is difficult because the antigenic peptides are unknown. Peptide library methods which include all possible peptide sequences offer a potentially powerful tool for the detection of cross-reactive antigenic peptides recognized by T cells. Here, we reduced the number of peptides per mixture by utilizing the known binding motifs of peptides for the HLA-DRB1*0405 molecule and evaluated the effectiveness of this library design. Each library mixture evoked a strong proliferative response in the unprimed peripheral blood lymphocytes (PBL) from HLA-DRB1*0405-positive donors but little or no response in the PBL from HLA-DRB1*0405-negative donors. The library also detected antigenic peptides that activated three antigen-specific T cell lines restricted by HLA-DRB1*0405, with different specificities. The motif-based approach thus presents a powerful method for monitoring T cells in large, heterogeneous T cell populations and is useful for the identification of the mimic peptide epitopes of T cell lines and clones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoimmune Diseases / immunology
  • Binding Sites
  • CD4-Positive T-Lymphocytes / immunology
  • Epitopes / chemistry*
  • Epitopes / metabolism
  • HLA-DR4 Antigen / genetics
  • HLA-DR4 Antigen / metabolism*
  • Humans
  • L Cells
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Peptide Library*
  • Peptides / chemistry
  • Peptides / immunology
  • Peptides / metabolism
  • Transfection

Substances

  • Epitopes
  • HLA-DR4 Antigen
  • Peptide Library
  • Peptides