Identification of an HLA-A*0201-restricted CD8+ T-cell epitope encoded within Leptospiral immunoglobulin-like protein A |
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| Authors: | Ying-Jun Guo Kai-Yu Wang Shu-Han Sun |
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| Institution: | 1. Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China;2. School of Life Sciences, Anhui University, Hefei, Anhui 230039, PR China;1. Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands;2. Department of Medicine, Dr. Kariadi Hospital, Faculty of Medicine, Diponegoro University, Semarang, Indonesia;3. Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;4. Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands;5. WHO/FAO/OIE and National Leptospirosis Reference Centre, KIT Biomedical Research, Amsterdam, The Netherlands;6. National Reference Laboratory for Leptospirosis, Dr. Kariadi Hospital, Semarang, Indonesia;7. Vetsuisse Faculty, University of Bern, Bern, Switzerland;8. ARTEMIS One Health Research Institute, Utrecht, The Netherlands;9. Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, United States;1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;2. Faculty of Veterinary Medicine, University of São Paulo, São Paulo, Brazil;3. Oswaldo Cruz Foundation, Salvador, Bahia, Brazil;4. Institut Pasteur, Biology of Spirochetes Unit, Paris, France;5. Department of Epidemiology of Microbial Diseases, Yale University, EUA, CT, USA;6. Laboratory of Bacteriology, Butantan Institute, São Paulo, Brazil;1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;2. Special Laboratory of Applied Toxinology, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, Brazil;3. Laboratory of Bacteriology, Butantan Institute, São Paulo, Brazil;3. From the Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Paul-Ehrlich-Strasse 40, D-60596 Frankfurt, Germany,;4. the Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40506,;5. the Institute of Biochemistry, Goethe University of Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt, Germany,;6. the Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstrasse 11a, D-07745 Jena, Germany,;12. the Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, D-69120 Heidelberg, Germany, and;8. Friedrich Schiller University, D-07743 Jena, Germany |
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| Abstract: | Leptospirosis is an important zoonosis in humans. Immunity against leptospiral infection was thought to be primarily humoral, and limited studies have addressed the role of CD8+ T cells. Leptospiral immunoglobulin-like protein A (LigA) is an important protective antigen of Leptospira and a potential target for Leptospira-specific cell-mediated immunity. In this study, twenty LigA-derived peptides were tested their binding affinity and stability for the HLA-A*0201 molecule. Peptides with high binding affinity and stability for HLA-A*0201 were then assessed their capacity to elicit specific cytotoxic T-lymphocyte (CTL) responses using cytotoxicity, ELISPOT assays for IFN-γ and HLA-A*0201-peptide tetramer assays. We identified a HLA-A*0201-restricted epitope, LigA305–313 KLIVTPAAL in Leptospira LigA. CTLs specific for LigA305–313 were elicited both in HLA-A2.1/Kb transgenic mice and in patients with a clinical and/or laboratory diagnosis of leptospirosis. Staining of the HLA-A*0201–LigA305–313 tetramer revealed the presence of LigA305–313-specific CTLs in peripheral blood mononuclear cells (PBMCs) sourced from five patients infected with three different serovars of Leptospira. In conclusion, we report the existence of specific cytotoxic CD8+ T cells in patients with leptospirosis and we suggest that the newly identified epitope, LigA305–313, will be helpful in enhancing the understanding of the mechanism of immunity to leptospirosis. |
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