title: Identification of an HLA-A*0201-restricted CD8(+) T-cell epitope encoded within Leptospiral immunoglobulin-like protein A.
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-gamma and HLA-A*0201-peptide tetramer assays. We identified a HLA-A*0201-restricted epitope, LigA(305-313) KLIVTPAAL in Leptospira LigA. CTLs specific for LigA(305-313) were elicited both in HLA-A2.1/K(b) transgenic mice and in patients with a clinical and/or laboratory diagnosis of leptospirosis. Staining of the HLA-A*0201-LigA(305-313) tetramer revealed the presence of LigA(305-313)-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, LigA(305-313), will be helpful in enhancing the understanding of the mechanism of immunity to leptospirosis.
authors.affiliation: Department of Medical Genetics, College of Basic Medical Sciences, Second Military Medical University, Xiangyin Road 800, Shanghai 200433, China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Guo
authors.forename: Kai-Yu
authors.initials: KY
authors.lastname: Wang
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Sun
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007919:Leptospira / Q000276:immunology*; D007922:Leptospirosis / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding
chemical_list: D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C487005:LigA-m protein, Leptospira interrogans