Identification and HLA restriction of naturally derived Th1-cell epitopes from the secreted Mycobacterium tuberculosis antigen 85B recognized by antigen-specific human CD4+ T-cell lines

被引:80
作者
Mustafa, AS
Shaban, FA
Abal, AT
Al-Attiyah, R
Wiker, HG
Lundin, KEA
Oftung, F
Huygen, K
机构
[1] Kuwait Univ, Fac Med, Dept Microbiol, Safat 13110, Kuwait
[2] Kuwait Univ, Fac Med, Dept Med, Safat 13110, Kuwait
[3] Minist Hlth, Chest Dis Hosp, Safat, Kuwait
[4] Univ Oslo, Natl Hosp, Inst Immunol, Oslo, Norway
[5] Natl Inst Publ Hlth, Dept Environm Med, Oslo, Norway
[6] Natl Inst Publ Hlth, Dept Vaccinol, Oslo, Norway
[7] Inst Pasteur, Brussels, Belgium
关键词
D O I
10.1128/IAI.68.7.3933-3940.2000
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Antigen 85B (Ag85B/MPT59) is a major secreted protein from Mycobacterium tuberculosis which is a promising candidate antigen for inclusion in novel subunit vaccines against tuberculosis (TB), The present study was undertaken to map naturally derived T-cell epitopes from M. tuberculosis Ag85B in relation to major histocompatibility complex (MHC) class II restriction. Antigen-specific CD4(+) T-cell lines were established from HLA-typed TB patients and Mycobacterium bovis BCG vaccinees by stimulation of peripheral blood mononuclear cells with purified Ag85B in vitro. The established T-cell lines were then tested for proliferation and gamma interferon (IFN-gamma) secretion in response to 31 overlapping synthetic peptides (18-mers) covering the entire sequence of the mature protein, The results showed that the epitopes recognized by T-cell lines from TB patients were scattered throughout the Ag85B sequence whereas the epitopes recognized by T-cell lines from BCC vaccinees were located toward the N-terminal part of the antigen. The T-cell epitopes represented by peptides p2 (amino acids [aa] 10 to 27), p3 (aa 19 to 36), and pll (aa 91 to 108) were frequently recognized by antigen-specific T-cell lines from BCG vaccinees in both proliferation and IFN-gamma assays. MHC restriction analysis demonstrated that individual T-cell lines specifically recognized the complete Ag85B either in association with one of the self HLA-DRB1, DRB3, or DRB4 gene products or nonspecifically in a promiscuous manner. At the epitope level, panel studies showed that peptides p2, p3, and p11 were presented to T cells by HLA-DR-matched as well as mismatched allogeneic antigen-presenting cells, thus representing promiscuous epitopes, The identification of naturally derived peptide epitopes from the M, tuberculosis Ag85B presented to Th1 cells in the context of multiple HLA-DR molecules strongly supports the relevance of this antigen to subunit vaccine design.
引用
收藏
页码:3933 / 3940
页数:8
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