scholarly journals New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Mariateresa Coppola ◽  
Krista E. van Meijgaarden ◽  
Kees L. M. C. Franken ◽  
Susanna Commandeur ◽  
Gregory Dolganov ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Cytokine Profiles ◽  
Human T Cell ◽  
Genome Wide

scholarly journals Human T-cell responses to secreted antigen fractions of Mycobacterium tuberculosis.

1995 ◽  
Vol 63 (4) ◽  
pp. 1491-1497 ◽  
Author(s):  
H Boesen ◽  
B N Jensen ◽  
T Wilcke ◽  
P Andersen
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Human T Cell

Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis

2006 ◽  
Vol 8 (8) ◽  
pp. 2052-2060 ◽  
Author(s):  
Eliane M.S. Leyten ◽  
May Young Lin ◽  
Kees L.M.C. Franken ◽  
Annemieke H. Friggen ◽  
Corine Prins ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Human T Cell

scholarly journals Normal Tissue Depresses While Tumor Tissue Enhances Human T Cell Responses In Vivo to a Novel Self/Tumor Melanoma Antigen, OA1

2003 ◽  
Vol 170 (3) ◽  
pp. 1579-1585 ◽  
Author(s):  
Christopher E. Touloukian ◽  
Wolfgang W. Leitner ◽  
Rhonda E. Schnur ◽  
Paul F. Robbins ◽  
Yong Li ◽  
...  
Keyword(s):  
T Cell ◽  
Normal Tissue ◽  
Tumor Tissue ◽  
T Cell Responses ◽  
Melanoma Antigen ◽  
Cell Responses ◽  
Human T Cell

scholarly journals T-Cell Recognition of the HspX Protein of Mycobacterium tuberculosis Correlates with Latent M. tuberculosis Infection but Not with M. bovis BCG Vaccination

2007 ◽  
Vol 75 (6) ◽  
pp. 2914-2921 ◽  
Author(s):  
Annemieke Geluk ◽  
May Young Lin ◽  
Krista E. van Meijgaarden ◽  
Eliane M. S. Leyten ◽  
Kees L. M. C. Franken ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Recognition ◽  
T Cell Epitopes ◽  
Bcg Vaccination ◽  
T Cell Recognition ◽  
Cell Responses

ABSTRACT During stationary growth or in vitro conditions mimicking relevant aspects of latency, the HspX protein (Rv2031c) is specifically upregulated by Mycobacterium tuberculosis. In this study we compared T-cell responses against HspX and the secreted M. tuberculosis protein Ag85B (Rv1886c) in tuberculosis (TB) patients, tuberculin skin test-positive individuals, M. bovis BCG-vaccinated individuals, and healthy negative controls. Gamma interferon responses to HspX were significantly higher in M. tuberculosis-exposed individuals than in M. tuberculosis-unexposed BCG vaccinees. In contrast, no such differences were found with respect to T-cell responses against Ag85B. Therefore, BCG-based vaccines containing relevant fragments of HspX may induce improved responses against this TB latency antigen. To identify relevant major histocompatibility complex class I- and class II-restricted HspX-specific T-cell epitopes, we immunized HLA-A2/Kb and HLA-DR3.Ab0 transgenic (tg) mice with HspX. Two new T-cell epitopes were identified, p91-105 and p31-50, restricted via HLA-A*0201 and HLA-DRB1*0301, respectively. These epitopes were recognized by human T cells as well, underlining the relevance of HspX T-cell recognition both in vivo and in vitro. In line with the data in humans, BCG immunization of both tg strains did not lead to T-cell responses against HspX-derived epitopes, whereas nonlatency antigens were efficiently recognized. These data support the notion that BCG vaccination per se does not induce T-cell responses against the latency antigen, HspX. Thus, we suggest that subunit vaccines incorporating HspX and/or other latency antigens, as well as recombinant BCG strains expressing latency antigens need to be considered as new vaccines against TB.

scholarly journals Human T-cell responses to the RD1-encoded protein TB27.4 (Rv3878) from Mycobacterium tuberculosis

Immunology ◽  
2003 ◽  
Vol 110 (4) ◽  
pp. 507-512 ◽  
Author(s):  
Else Marie Agger ◽  
Inger Brock ◽  
Limei Meng Okkels ◽  
Sandra M. Arend ◽  
Claus S. Aagaard ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Human T Cell

scholarly journals Naive Human T Cells Develop into Th1 Effectors after Stimulation with Mycobacterium tuberculosis-Infected Macrophages or Recombinant Ag85 Proteins

2000 ◽  
Vol 68 (12) ◽  
pp. 6826-6832 ◽  
Author(s):  
Donna M. Russo ◽  
Natalia Kozlova ◽  
David L. Lakey ◽  
Douglas Kernodle
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Interleukin 12 ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cell Responses ◽  
Human T Cell ◽  
Human T Cells

ABSTRACT Most studies of human T-cell responses in tuberculosis have focused on persons with either active disease or latent infection. Although this work has been critical in defining T-cell correlates of successful versus failed host containment, little is known about the development of Mycobacterium-specific T-cell responses in uninfected persons. To explore this issue, naive T cells from uninfected donors were sensitized in vitro with avirulent Mycobacterium tuberculosis-infected autologous macrophages. T-cell lines primed in this manner proliferated and produced cytokines after challenge with mycobacterial antigens. Of 11 such lines, 8 were high Th1 responders, 2 were low Th1 responders, and 1 was a Th2 responder. Furthermore, similar patterns and magnitudes of proliferative and cytokine responses were seen when Mycobacterium infection-primed lines were challenged with recombinant antigen 85 (Ag85) proteins. The addition of interleukin 12 (IL-12) during the initial sensitization increased the magnitude of Th1 responses; however, antibody to IL-12 did not eliminate Th1 responses, suggesting that additional factors contributed to the differentiation of these cells. Finally, in the presence of IL-12, recombinant Ag85B was able to prime naive T cells for Th1 responses upon challenge with Mycobacterium-infected macrophages or Ag85B. Therefore, under the appropriate conditions, priming with whole bacteria or a subunit antigen can stimulateMycobacterium-specific Th1 effector cell development. Further definition of the antigens and conditions required to drive naive human T cells to differentiate into Th1 effectors should facilitate the development of an improved tuberculosis vaccine.

scholarly journals Molecular Characterization and Human T-Cell Responses to a Member of a Novel Mycobacterium tuberculosis mtb39Gene Family

1999 ◽  
Vol 67 (6) ◽  
pp. 2941-2950 ◽  
Author(s):  
Davin C. Dillon ◽  
Mark R. Alderson ◽  
Craig H. Day ◽  
David M. Lewinsohn ◽  
Rhea Coler ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Molecular Characterization ◽  
Mononuclear Cells ◽  
Cell Clone ◽  
Bacterial Load ◽  
T Cell Responses ◽  
Cell Responses ◽  
Human T Cell ◽  
T Cell Clone

ABSTRACT We have used expression screening of a genomic Mycobacterium tuberculosis library with tuberculosis (TB) patient sera to identify novel genes that may be used diagnostically or in the development of a TB vaccine. Using this strategy, we have cloned a novel gene, termed mtb39a, that encodes a 39-kDa protein. Molecular characterization revealed that mtb39a is a member of a family of three highly related genes that are conserved among strains of M. tuberculosis and Mycobacterium bovis BCG but not in other mycobacterial species tested. Immunoblot analysis demonstrated the presence of Mtb39A in M. tuberculosis lysate but not in culture filtrate proteins (CFP), indicating that it is not a secreted antigen. This conclusion is strengthened by the observation that a human T-cell clone specific for purified recombinant Mtb39A protein recognized autologous dendritic cells infected with TB or pulsed with purified protein derivative (PPD) but did not respond to M. tuberculosis CFP. Purified recombinant Mtb39A elicited strong T-cell proliferative and gamma interferon responses in peripheral blood mononuclear cells from 9 of 12 PPD-positive individuals tested, and overlapping peptides were used to identify a minimum of 10 distinct T-cell epitopes. Additionally, mice immunized with mtb39a DNA have shown increased protection from M. tuberculosis challenge, as indicated by a reduction of bacterial load. The human T-cell responses and initial animal studies provide support for further evaluation of this antigen as a possible component of a subunit vaccine for M. tuberculosis.

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