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Human Th1 Cell Lines Recognize the Mycobacterium tuberculosis ESAT‐6 Antigen and its Peptides in Association with Frequently Expressed HLA Class II Molecules
Author(s) -
Mustafa A. S.,
Shaban F. A.,
AlAttiyah R.,
Abal A. T.,
ElShamy A. M.,
Andersen P.,
Oftung F.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01204.x
Subject(s) - esat 6 , cytotoxic t cell , human leukocyte antigen , antigen , epitope , antigen presentation , major histocompatibility complex , biology , t cell , antigen presenting cell , antigen processing , mhc class ii , immunology , mhc restriction , microbiology and biotechnology , virology , mhc class i , immune system , in vitro , genetics , recombinant dna , gene
We have used a synthetic‐peptide approach to map epitope regions of the Mycobacterium tuberculosis ESAT‐6 antigen recognized by human T cells in relation to major histocompatibility complex (MHC) restriction. ESAT‐6‐specific CD4 + T‐cell lines were established by stimulating peripheral blood mononuclear cells from 25 HLA‐DR‐typed tuberculosis patients with complete antigen in vitro . The established T‐cell lines were then screened for proliferation and interferon‐γ (IFN‐γ) secretion in response to eight overlapping 20‐mer peptides covering the ESAT‐6 sequence. The response of the T‐cell lines to ESAT‐6 and peptides from a human leucocyte antigen (HLA)‐heterogeneous group of donors suggested the presence of multiple epitopes and promiscuous recognition of the antigen. Analysis of antigen and peptide recognition in the presence of anti‐HLA class I and class II antibodies suggested that the T‐cell lines recognized ESAT‐6 in association with HLA‐DR and ‐DQ molecules. Furthermore, testing of selected T‐cell lines with ESAT‐6 and the peptides in the presence of autologous and allogeneic HLA‐DR‐ and ‐DQ‐typed antigen‐presenting cells identified HLA‐DR2, ‐DR52 and ‐DQ2 amongst the HLA molecules involved in the presentation of ESAT‐6 and its peptides to human Th1 cells. In addition, the T‐cell lines were cytotoxic for monocytes and macrophages pulsed with ESAT‐6 and peptides. In conclusion, the recognition of ESAT‐6 by IFN‐γ‐secreting and cytotoxic CD4 + T cells in association with frequently expressed HLA class II molecules supports the application of this antigen to either specific diagnosis or subunit vaccine design.