title: A broad profile of co-dominant epitopes shapes the peripheral Mycobacterium tuberculosis specific CD8+ T-cell immune response in South African patients with active tuberculosis.
abstract: We studied major histocompatibility complex (MHC) class I peptide-presentation and nature of the antigen-specific CD8+ T-cell response from South African tuberculosis (TB) patients with active TB. 361 MHC class I binding epitopes were identified from three immunogenic TB proteins (ESAT-6 [Rv3875], Ag85B [Rv1886c], and TB10.4 [Rv0288], including amino acid variations for Rv0288, i.e., A10T, G13D, S27N, and A71S for MHC allotypes common in a South African population (e.g., human leukocyte antigen [HLA]-A*30, B*58, and C*07). Inter-allelic differences were identified regarding the broadness of the peptide-binding capacity. Mapping of frequencies of Mycobacterium tuberculosis (M. tb) antigen-specific CD8+ T-cells using 48 different multimers, including the newly constructed recombinant MHC class I alleles HLA-B*58:01 and C*0701, revealed a low frequency of CD8+ T-cell responses directed against a broad panel of co-dominant M. tb epitopes in the peripheral circulation of most patients. The antigen-specific responses were dominated by CD8+ T-cells with a precursor-like phenotype (CD45RA+CCR7+). The data show that the CD8+ T-cell response from patients with pulmonary TB (prior to treatment) is directed against subdominant epitopes derived from secreted and non-secreted M. tb antigens and that variant, natural occurring M. tb Rv0288 ligands, have a profound impact on T-cell recognition.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Axelsson-Robertson
authors.forename: André G
authors.initials: AG
authors.lastname: Loxton
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Marthie M
authors.initials: MM
authors.lastname: Ehlers
authors.forename: Marleen M
authors.initials: MM
authors.lastname: Kock
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015235:HLA-B Antigens / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013019:South Africa; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; D015236:HLA-C Antigens
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