title: Identification of Mycobacterium tuberculosis PPE68-specific HLA-A*0201-restricted epitopes for tuberculosis diagnosis.
abstract: PPE68 is a Mycobacterium tuberculosis-specific protein which is absent from the vaccine strains of BCG. A panel of 14 PPE68-derived peptides predicted to bind to HLA-A*0201 was synthesized. The HLA-A*0201 restriction of these peptides was determined in T2 cell line and HLA-A*0201 transgenic mice. The specificity of peptides was assessed in pulmonary tuberculosis (TB) patients using IFN-γ enzyme-linked immunospot (ELISPOT) assay, and immunodominant peptides were further used to evaluate their diagnostic potential in HLA-A*0201-positive pulmonary TB patients. 13 out of 14 peptides were identified as high-affinity binders. Of these peptides, 12 peptides induced significant IFN-γ-secreting T cell response in transgenic mice and 9 peptides were efficiently recognized by peripheral blood mononuclear cells of 10 HLA-A*0201-positive TB patients. Four immunodominant HLA-A*0201-restricted epitopes (PPE68126-134, PPE68133-141, PPE68140-148, and PPE68148-156) were recognized by the most of 80 HLA-A*0201-positive TB patients (81, 86, 74, and 84 %, respectively). These epitopes may be used for a potential diagnosis of M. tuberculosis infection.
authors: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors: Zhi-Liang
authors: ZL
authors: Duan
authors: Qiang
authors: Q
authors: Li
authors: Sina
authors: S
authors: Wang
authors: Xin-Yu
authors: XY
authors: Chen
authors: Hui-Fang
authors: HF
authors: Liu
authors: Bo-Kun
authors: BK
authors: Chen
authors: De-Zhou
authors: DZ
authors: Li
authors: Xi
authors: X
authors: Huang
authors: Jin-Sheng
authors: JS
authors: Wen
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000175:diagnosis* / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C528814:PPE68 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma