title: MHC class II tetramer guided detection of Mycobacterium tuberculosis-specific CD4+ T cells in peripheral blood from patients with pulmonary tuberculosis.
abstract: Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition to the more than 100-year-old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4 tetrameric complexes to visualize ex vivo CD4(+) T cells directed against the antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and other Mycobacterium species, and CD4(+) T cells which recognize the MTB-associated ESAT-6 antigen. MTB-reactive CD4(+) T cells reside predominantly in the CD45RA(+) CD28(+) and CD45(-) CD28(+) T-cell subset and recognize naturally processed and presented MTB epitopes. HLA-DR4-restricted, Ag85B or ESAT-6-specific CD4(+) T cells show similar dynamics over time in peripheral blood mononuclear cells (PBMC) when compared with CD8(+) T cells directed against the corresponding HLA-A2-presented MTB epitopes in patients with pulmonary MTB infection and subsequent successful therapy. This was not found to be true for T-cell responses directed against the 19-kDa lipoprotein. The dissection of the cellular immune response in M. tuberculosis infection will enable novel strategies for monitoring MTB vaccine candidates and to gauge CD4(+) T cells directed against MTB.
authors: Department of Medical Microbiology, University of Mainz, Hochhaus Augustusplatz, Mainz, Germany.
authors: H
authors: H
authors: Höhn
authors: C
authors: C
authors: Kortsik
authors: I
authors: I
authors: Zehbe
authors: W E
authors: WE
authors: Hitzler
authors: K
authors: K
authors: Kayser
authors: K
authors: K
authors: Freitag
authors: C
authors: C
authors: Neukirch
authors: P
authors: P
authors: Andersen
authors: T M
authors: TM
authors: Doherty
authors: M
authors: M
authors: Maeurer
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D018984:Epitopes, T-Lymphocyte / Q000097:blood*; D000949:Histocompatibility Antigens Class II / Q000097:blood* / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II