Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection
Identification of HLA-restricted peptides derived from mycobacterial antigens that are endowed with high affinity and strong antigenicity is not only of interest in tuberculosis (TB) diagnostics and treatment efficacy evaluation, but might also provide potential candidates for the development of the...
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.03131/full |
| _version_ | 1818475733156102144 |
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| author | Yuan-yong Liu Yuan-yong Liu Wei Sha Shiqiang Xu Xu-wei Gui Liliang Xia Ping Ji Shujun Wang Guo-ping Zhao Xiao Zhang Yingying Chen Ying Wang Ying Wang |
| author_facet | Yuan-yong Liu Yuan-yong Liu Wei Sha Shiqiang Xu Xu-wei Gui Liliang Xia Ping Ji Shujun Wang Guo-ping Zhao Xiao Zhang Yingying Chen Ying Wang Ying Wang |
| author_sort | Yuan-yong Liu |
| collection | DOAJ |
| description | Identification of HLA-restricted peptides derived from mycobacterial antigens that are endowed with high affinity and strong antigenicity is not only of interest in tuberculosis (TB) diagnostics and treatment efficacy evaluation, but might also provide potential candidates for the development of therapeutic vaccines against drug-resistant TB. Our previous work demonstrated that lipoprotein Z (LppZ) displayed high immunogenicity and antigenicity in active TB patients. In the present study, ten HLA-A2-restricted LppZ peptides (LppZp1-10) were predicted by bioinformatics, among which LppZp7 and LppZp10 were verified to possess high affinity to HLA-A2 molecules using T2 cell-based affinity binding assay. Moreover, results from ELISpot assay showed that both LppZp7 and LppZp10 peptides were able to induce more IFN-γ producing cells upon ex vivo stimulation of PBMC from HLA-A2+ active TB (ATB) patients as compared to those from healthy controls (HCs). Also, the numbers of LppZp7 and LppZp10-specific IFN-γ producing cells exhibited positive correlations with those of ESAT-6 peptide (E6p) or CFP-10 peptide (C10p) in ATB. Interestingly, stimulation with LppZp7/p10 mixture was able to induce higher intracellular expression of IFN-γ and IL-2 cytokines in CD8+ and CD4+ T cells from ATB as compared to HC, associated with lower expression of TNF-α in both CD8+ and CD4+ T cells. Taken together, HLA-A2-restricted LppZp7 and LppZp10 peptides display high immunoreactivity in HLA-matched ATB patients demonstrated by high responsiveness in both CD8+ and CD4+ T cells. With the ability to induce strong antigen-specific cellular responses, LppZp7 and LppZp10 are of potential value for the future applications in the prevention and control of TB. |
| first_indexed | 2024-12-10T09:16:29Z |
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| id | doaj.art-83484b8335dc4b27ae6e3f73b05c7d71 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-10T09:16:29Z |
| publishDate | 2018-12-01 |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-83484b8335dc4b27ae6e3f73b05c7d712022-12-22T01:54:51ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-12-01910.3389/fmicb.2018.03131347769Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis InfectionYuan-yong Liu0Yuan-yong Liu1Wei Sha2Shiqiang Xu3Xu-wei Gui4Liliang Xia5Ping Ji6Shujun Wang7Guo-ping Zhao8Xiao Zhang9Yingying Chen10Ying Wang11Ying Wang12School of Life Science and Technology, Changchun University of Science and Technology, Changchun, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaClinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaClinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, ChinaSchool of Life Science and Technology, Changchun University of Science and Technology, Changchun, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, ChinaIdentification of HLA-restricted peptides derived from mycobacterial antigens that are endowed with high affinity and strong antigenicity is not only of interest in tuberculosis (TB) diagnostics and treatment efficacy evaluation, but might also provide potential candidates for the development of therapeutic vaccines against drug-resistant TB. Our previous work demonstrated that lipoprotein Z (LppZ) displayed high immunogenicity and antigenicity in active TB patients. In the present study, ten HLA-A2-restricted LppZ peptides (LppZp1-10) were predicted by bioinformatics, among which LppZp7 and LppZp10 were verified to possess high affinity to HLA-A2 molecules using T2 cell-based affinity binding assay. Moreover, results from ELISpot assay showed that both LppZp7 and LppZp10 peptides were able to induce more IFN-γ producing cells upon ex vivo stimulation of PBMC from HLA-A2+ active TB (ATB) patients as compared to those from healthy controls (HCs). Also, the numbers of LppZp7 and LppZp10-specific IFN-γ producing cells exhibited positive correlations with those of ESAT-6 peptide (E6p) or CFP-10 peptide (C10p) in ATB. Interestingly, stimulation with LppZp7/p10 mixture was able to induce higher intracellular expression of IFN-γ and IL-2 cytokines in CD8+ and CD4+ T cells from ATB as compared to HC, associated with lower expression of TNF-α in both CD8+ and CD4+ T cells. Taken together, HLA-A2-restricted LppZp7 and LppZp10 peptides display high immunoreactivity in HLA-matched ATB patients demonstrated by high responsiveness in both CD8+ and CD4+ T cells. With the ability to induce strong antigen-specific cellular responses, LppZp7 and LppZp10 are of potential value for the future applications in the prevention and control of TB.https://www.frontiersin.org/article/10.3389/fmicb.2018.03131/fulltuberculosismycobacterial lipoprotein ZHLA-A2-restricted peptideantigenicityCD8+ and CD4+ T cells responses |
| spellingShingle | Yuan-yong Liu Yuan-yong Liu Wei Sha Shiqiang Xu Xu-wei Gui Liliang Xia Ping Ji Shujun Wang Guo-ping Zhao Xiao Zhang Yingying Chen Ying Wang Ying Wang Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection Frontiers in Microbiology tuberculosis mycobacterial lipoprotein Z HLA-A2-restricted peptide antigenicity CD8+ and CD4+ T cells responses |
| title | Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection |
| title_full | Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection |
| title_fullStr | Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection |
| title_full_unstemmed | Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection |
| title_short | Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection |
| title_sort | identification of hla a2 restricted mycobacterial lipoprotein z peptides recognized by t cellsfrom patients with activetuberculosis infection |
| topic | tuberculosis mycobacterial lipoprotein Z HLA-A2-restricted peptide antigenicity CD8+ and CD4+ T cells responses |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.03131/full |
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