Longitudinal analysis of Mycobacterium tuberculosis 19-kDa antigen-specific T cells in patients with pulmonary tuberculosis: association with disease activity and cross-reactivity to a peptide from HIVenv gp120.
CD8(+) T cells play a central role in immune protection against infection with Mycobacterium tuberculosis. One of the target epitopes for anti-M. tuberculosis directed CD8(+) T cells is the HLA-A2-restricted 19-kDa lipoprotein peptide VLTDGNPPEV. T cell clones directed against this epitope recognized not only the nominal peptide ligand, but also a closely related peptide (VPTDPNPPEV) from the HIV envelope gp120 (HIV(env) gp120) protein characterized by IFN-gamma release. This cross-reactivity was confirmed in ex vivo in M. tuberculosis 19-kDa tetramer-sorted T cells from patients with tuberculosis and in HIVgp120 tetramer-reactive T cells sorted from HIV(+) patients. M. tuberculosis 19-kDa antigen-reactive T cells were present in HLA-A2(+) patients (10/10) with HIV infection with no evidence of M. tuberculosis infection, but they are absent in peripheral blood lymphocytes from healthy HLA-A2(+) individuals (10/10). M. tuberculosis 19-kDa antigen-reactive T cells were elevated in acute pulmonary tuberculosis, declined with response to therapy (7/10 patients) and resided in the terminally differentiated CD8(+) T cell subset. CD8(+) cross-reactive T cells recognizing HIV(env) or M. tuberculosis 19-kDa antigens may contribute to pathogenesis in individuals co-infected with both pathogens and may also present a marker for active tuberculosis.
Höhn
Hanni
H
Department of Medical Microbiology, University of Mainz, Germany.
Kortsik
Cornelius
C
Tully
Glenn
G
Nilges
Katja
K
Necker
Antje
A
Freitag
Kirsten
K
Neukirch
Claudia
C
Galle
Peter
P
Löhr
Hans
H
Maeurer
Markus J
MJ
D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD; D001426:Bacterial Proteins / Q000276:immunology*; D015415:Biomarkers; D051929:CD146 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008137:Longitudinal Studies; D008562:Membrane Glycoproteins / Q000276:immunology; D018716:Molecular Mimicry; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D019006:Neural Cell Adhesion Molecules; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000150:complications / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
C087864:19 kDa antigen, Mycobacterium; D000942:Antigens, Bacterial; D015703:Antigens, CD; D001426:Bacterial Proteins; D015415:Biomarkers; D051929:CD146 Antigen; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D014764:Viral Proteins; C076036:oncogene protein E2, Human papillomavirus type 1; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor