Ulrichs T, Munk M E, Mollenkopf H, Behr-Perst S, Colangeli R, Gennaro M L, Kaufmann S H
Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany.
Eur J Immunol. 1998 Dec;28(12):3949-58. doi: 10.1002/(SICI)1521-4141(199812)28:12<3949::AID-IMMU3949>3.0.CO;2-4.
Vaccination against and diagnosis of tuberculosis are still insufficient. Proteins secreted by Mycobacterium tuberculosis induce strong immune responses in tuberculosis and constitute prime candidates for development of novel vaccines against tuberculosis as well as for immunodiagnostic assays. We investigated the role of the secreted proteins MPT63, MPT64 and ESAT6 from M. tuberculosis in healthy individuals and tuberculosis patients. None of the secreted proteins stimulated peripheral blood mononuclear cells from healthy donors. In contrast, CD4+ T cells from many tuberculosis patients were stimulated in an MHC class II-restricted fashion by ESAT6, but not by MPT63 or MPT64. T cell reactivities of tuberculosis patients were focused on the N-terminal region of ESAT6. The ESAT6 T cell epitopes were presented by different HLA-DR phenotypes. Cell cultures responding to either ESAT6 or synthetic peptides thereof showed mRNA transcripts for macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic protein (MCP)-1 or IL-8 and production of IFN-gamma and MIP-1alpha. Our results suggest that the secreted M. tuberculosis proteins MPT63, MPT64 or ESAT6 do not stimulate unprimed T cells, and that ESAT6 may be a potential candidate antigen for detection of clinical disease.
结核病的疫苗接种和诊断仍存在不足。结核分枝杆菌分泌的蛋白质在结核病中可诱导强烈的免疫反应，是开发新型结核病疫苗以及免疫诊断检测方法的主要候选对象。我们研究了结核分枝杆菌分泌蛋白MPT63、MPT64和ESAT6在健康个体和结核病患者中的作用。这些分泌蛋白均未刺激健康供体的外周血单核细胞。相比之下，许多结核病患者的CD4 + T细胞受到ESAT6以MHC II类限制方式的刺激，但未受到MPT63或MPT64的刺激。结核病患者的T细胞反应性集中在ESAT6的N端区域。ESAT6 T细胞表位由不同的HLA - DR表型呈递。对ESAT6或其合成肽有反应的细胞培养物显示出巨噬细胞炎性蛋白（MIP）-1α、单核细胞趋化蛋白（MCP）-1或IL - 8的mRNA转录本以及IFN - γ和MIP - 1α的产生。我们的结果表明，结核分枝杆菌分泌蛋白MPT63、MPT64或ESAT6不会刺激未致敏的T细胞，并且ESAT6可能是检测临床疾病的潜在候选抗原。
