Open AccessIdentification of HLA ‐A*11:01‐restricted Mycobacterium tuberculosis CD 8 + T cell epitopes
Author(s) -
Liu SuDong,
Su Jin,
Zhang ShiMeng,
Dong HaiPing,
Wang Hui,
Luo Wei,
Wen Qian,
He JianChun,
Yang XiaoFan,
Ma Li
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12867
Subject(s) - epitope , mycobacterium tuberculosis , antigen , t cell , human leukocyte antigen , biology , immune system , peripheral blood mononuclear cell , tuberculosis , virology , cytotoxic t cell , immunology , microbiology and biotechnology , in vitro , medicine , biochemistry , pathology
New vaccines are needed to combat Mycobacterium tuberculosis ( MTB ) infections. The currently employed Bacillus Calmette‐Guérin vaccine is becoming ineffective, due in part to the emergence of multidrug‐resistant tuberculosis ( MDR ‐ TB ) strains and the reduced immune capacity in cases of HIV coinfection. CD 8 + T cells play an important role in the protective immunity against MTB infections, and the identification of immunogenic CD 8 + T cell epitopes specific for MTB is essential for the design of peptide‐based vaccines. To identify CD 8 + T cell epitopes of MTB proteins, we screened a set of 94 MTB antigens for HLA class I A*11:01‐binding motifs. HLA ‐A*11:01 is one of the most prevalent HLA molecules in Southeast Asians, and definition of T cell epitopes it can restrict would provide significant coverage for the Asian population. Peptides that bound with high affinity to purified HLA molecules were subsequently evaluated in functional assays to detect interferon‐γ release and CD 8 + T cell proliferation in active pulmonary TB patients. We identified six novel epitopes, each derived from a unique MTB antigen, which were recognized by CD 8 + T cells from active pulmonary TB patients. In addition, a significant level of epitope‐specific T cells could be detected ex vivo in peripheral blood mononuclear cells from active TB patients by an HLA ‐A*11:01 dextramer carrying the peptide Rv3130c 194‐204 (from the MTB triacylglycerol synthase Tgs1), which was the most frequently recognized epitope in our peptide library. In conclusion, this study identified six dominant CD 8 + T cell epitopes that may be considered potential targets for subunit vaccines or diagnostic strategies against TB .