Identification of HLA-A24-binding peptides of Mycobacterium tuberculosis derived proteins with beta 2m linked HLA-A24 single chain expressing cells.
Tuberculosis is caused by an intracellular pathogen Mycobacterium tuberculosis (Mtb) and poses a persistent threat to global health. MHC class I-restricted CD8 cytotoxic T lymphocytes (CTL) are essential for protective immunity to Tuberculosis. Information for CTL epitopes derived from Mtb is desirable for vaccine design and assessment of T cell responses. However, the knowledge about CTL epitopes of Mtb, particularly those non-A2 HLA alleles restricted is rare. In this study, beta-2-microglobulin (beta 2m, beta(2)m) linked HLA-A24 single chain was expressed on RMA-S cell line defective in the endogenous antigen processing and applied for screening of peptides which could stabilize the HLA-A24 complex on the cell surface. From a group of peptides predicted as binders by a computer algorithm, five peptides were shown to bind to HLA-A24 protein on the cell surface. As comparison we have also identified a dozen Mtb proteins derived peptides that bind to HLA-A2 specifically. The cell line and HLA binders present here would be useful for further identification of CD8 restricted Mtb epitopes.
Ding
Jie
J
CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Chinese Academy of Sciences, Beijing, China.
Wang
Yan
Y
Cheng
Tingting
T
Chen
Xiaowei
X
Gao
Bin
B
D000465:Algorithms; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003198:Computer Simulation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D059871:HLA-A24 Antigen; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D032581:Tuberculosis Vaccines / Q000276:immunology; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D010446:Peptide Fragments; D032581:Tuberculosis Vaccines; D001613:beta 2-Microglobulin