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 |
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Authors: | Takeshi Tana Nobuhiro Kamikawaji Christopher J Savoie Tohru Sudo Yurika Kinoshita T Sasazuki |
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Institution: | (1) Department of Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan Tel. +81-92-642-6827; Fax +81-92-632-0150 e-mail: sasazuki@bioreg.kyushu-u.ac.jp, JP |
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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.
Received: October 3, 1997 / Accepted: October 23, 1997 |
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Keywords: | Peptide library Binding motif HLA HLA-DRB1*0405 T cell epitope |
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