title: The diagnostic potential of MPT63-derived HLA-A*0201-restricted CD8+ T-cell epitopes for active pulmonary tuberculosis.
abstract: MPT63 protein is found only in Mycobacterium tuberculosis complex, including M. tuberculosis and M. bovis. Detection of MPT63-specific IFN-γ-secreting T cells could be useful for the diagnosis of tuberculosis (TB) diseases. In the present study, the HLA-A*0201 restriction of ten predicted MPT63-derived CD8(+) T-cell epitopes was assessed on the basis of T2 cell line and HLA-A*0201 transgenic mice. The diagnostic potential of immunogenic peptides in active pulmonary TB patients was evaluated using an IFN-γ enzyme-linked immunospot assay. It was found that five peptides bound to HLA-A*0201 with high affinity, whereas the remaining peptides exhibited low affinity for HLA-A*0201. Five immunogenic peptides (MPT6318-26 , MPT6329-37 , MPT6320-28 , MPT635-14 and MPT6310-19 ) elicited large numbers of cytotoxic IFN-γ-secreting T cells in HLA-A*0201 transgenic mice. Each of the five immunogenic peptides was recognized by peripheral blood mononuclear cells from 45% to 73% of 40 HLA-A*0201 positive TB patients. The total diagnostic sensitivity of the five immunogenic peptides was higher than that of a T-SPOT.TB assay (based on ESAT-6 and CFP-10) (93% versus 90%). It is noticeable that the diagnostic sensitivity of the combination of five immunogenic peptides and T-SPOT.TB assay reached 100%. These MPT63-derived HLA-A*0201-restricted CD8(+) T-cell epitopes would likely contribute to the immunological diagnosis of M. tuberculosis infection and may provide the components for designing an effective TB vaccine.
authors.affiliation: Department of Clinical Laboratory, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000.|Department of Liver Disease, Second People's Hospital of Ningbo, Ningbo 315010.
authors.forename: Dezhou
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000.|Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000.|Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road.|Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000.|Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000.|Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000.
authors.forename: Bokun
authors.initials: B
authors.lastname: Chen
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000.|Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 325000, China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000097:blood / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000097:blood / Q000276:immunology; D011897:Random Allocation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C103339:MPT63 antigen, Mycobacterium tuberculosis; D010455:Peptides; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma
keywords: CD8+T-cell epitope; HLA-A*0201; MPT63; Mycobacterium tuberculosis