The identification of CD4+ T cell epitopes with dedicated synthetic peptide libraries

被引:91
作者
Hiemstra, HS
Duinkerken, G
Benckhuijsen, WE
Amons, R
deVries, RRP
Roep, BO
Drijfhout, JW
机构
[1] UNIV LEIDEN HOSP,IMMUNOHEMATOL & BLOOD BANK,NL-2300 RC LEIDEN,NETHERLANDS
[2] LEIDEN UNIV,DEPT BIOCHEM MED,SYLVIUS LAB,NL-2300 RC LEIDEN,NETHERLANDS
关键词
insulin-dependent diabetes mellitus;
D O I
10.1073/pnas.94.19.10313
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
For a large number of T cell-mediated immunopathologies, the disease-related antigens are not yet identified. Identification of T cell epitopes is of crucial importance for the development of immune-intervention strategies. We show that CD4(+) T cell epitopes can be defined by using a new system for synthesis and screening of synthetic peptide libraries. These Libraries are designed to bind to the HLA class II restriction molecule of the CD4(+) T cell clone of interest. The screening is based on three selection rounds using partial release of 14-mer peptides from synthesis beads and subsequent sequencing of the remaining peptide attached to the bead. With this approach, two peptides were identified that stimulate the beta cell-reactive CD4(+) T cell clone 1c10, which was isolated from a newly diagnosed insulin-dependent diabetes mellitus patient. After performing amino acid-substitution studies and protein database searches, a Haemophilus influenzae TonB-derived peptide was identified that stimulates clone 1c10. The relevance of this finding for the pathogenesis of insulin-dependent diabetes mellitus is currently under investigation. We conclude that this system is capable of determining epitopes for (autoreactive) CD4(+) T fell clones with previously unknown peptide specificity, This offers the possibility to define (auto)antigens by searching protein databases and/or to induce tolerance by using the peptide sequences identified. In addition the peptides might be used as leads to develop T cell receptor antagonists or anergy-inducing compounds.
引用
收藏
页码:10313 / 10318
页数:6
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