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

Susceptibility to a series of autoimmune diseases is strongly associat ed with particular HLA class II alleles. Identification of T cell clon es 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 cl ones in autoimmune diseases is difficult because the antigenic peptide s are unknown. Peptide library methods which include all possible pept ide sequences offer a potentially powerful tool for the detection of c ross-reactive antigenic peptides recognized by T cells. Here, we reduc ed the number of peptides per mixture by utilizing the known binding m otifs of peptides for the HLA-DRB10405 molecule and evaluated the eff ectiveness of this library design. Each library mixture evoked a stron g proliferative response in the unprimed peripheral blood lymphocytes (PBL) from HLA-DRB10405-positive donors but little or no response in the PBL from HLA-DRB10405-negative donors. The library also detected antigenic peptides that activated three antigen-specific T cell lines restricted by HLA-DRB10405, with different specificities. The motif-b ased approach thus presents a powerful method for monitoring T cells i n large, heterogeneous T cell populations and is useful for the identi fication of the mimic peptide epitopes of T cell lines and clones.