scholarly journals Phagosomal Processing of Mycobacterium tuberculosis Antigen 85B Is Modulated Independently of Mycobacterial Viability and Phagosome Maturation

2005 ◽  
Vol 73 (2) ◽  
pp. 1097-1105 ◽  
Author(s):  
Lakshmi Ramachandra ◽  
Jamie L. Smialek ◽  
Sam S. Shank ◽  
Marilyn Convery ◽  
W. Henry Boom ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Hybridoma Cells ◽  
Phagosome Maturation ◽  
Radiation Processing ◽  
Murine Bone Marrow ◽  
Mhc Ii ◽  
Tuberculosis Antigen ◽  
Class Ii Mhc ◽  
Mycobacterium Tuberculosis Antigen

ABSTRACT Control of Mycobacterium tuberculosis infection requires CD4 T-cell responses and major histocompatibility complex class II (MHC-II) processing of M. tuberculosis antigens (Ags). We have previously demonstrated that macrophages process heat-killed (HK) M. tuberculosis more efficiently than live M. tuberculosis. These observations suggested that live M. tuberculosis may inhibit Ag processing by inhibiting phagosome maturation or that HK M. tuberculosis may be less resistant to Ag processing. In the present study we examined the correlation between M. tuberculosis viability and phagosome maturation and efficiency of Ag processing. Since heat treatment could render M. tuberculosis Ags more accessible to proteolysis, M. tuberculosis was additionally killed by antibiotic treatment and radiation. Processing of HK, live, radiation-killed (RadK), or rifampin-killed (RifK) M. tuberculosis in activated murine bone marrow macrophages was examined by using an I-Ab-restricted T-cell hybridoma cell line (BB7) that recognizes an epitope derived from Ag 85B. Macrophages processed HK M. tuberculosis more rapidly and efficiently than they processed live, RadK, or RifK M. tuberculosis. Live, RadK, and RifK M. tuberculosis cells were processed with similar efficiencies for presentation to BB7 T hybridoma cells. Furthermore, phagosomes containing live or RadK M. tuberculosis expressed fewer M. tuberculosis peptide-MHC-II complexes than phagosomes containing HK M. tuberculosis expressed. Since only live M. tuberculosis was able to prevent acidification of the phagosome, our results suggest that regulation of phagosome maturation does not explain the differences in processing of different forms of M. tuberculosis. These findings suggest that the mechanisms used by M. tuberculosis to inhibit phagosomal maturation differ from the mechanisms involved in modulating phagosome Ag processing.

scholarly journals Phagosomal Processing of Mycobacterium tuberculosis Antigen 85B Is Modulated Independently of Mycobacterial Viability and Phagosome Maturation

2006 ◽  
Vol 74 (1) ◽  
pp. 802-802
Author(s):  
Lakshmi Ramachandra ◽  
Jamie L. Smialek ◽  
Sam S. Shank ◽  
Marilyn Convery ◽  
W. Henry Boom ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Phagosome Maturation ◽  
Tuberculosis Antigen ◽  
Antigen 85B ◽  
Mycobacterium Tuberculosis Antigen

scholarly journals Mycobacterium tuberculosis Synergizes with ATP To Induce Release of Microvesicles and Exosomes Containing Major Histocompatibility Complex Class II Molecules Capable of Antigen Presentation

2010 ◽  
Vol 78 (12) ◽  
pp. 5116-5125 ◽  
Author(s):  
Lakshmi Ramachandra ◽  
Yan Qu ◽  
Ying Wang ◽  
Colleen J. Lewis ◽  
Brian A. Cobb ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Hybridoma Cells ◽  
Complex Class ◽  
Mhc Ii ◽  
Histocompatibility Complex

ABSTRACT Major histocompatibility complex class II (MHC-II) molecules are released by murine macrophages upon lipopolysaccharide (LPS) stimulation and ATP signaling through the P2X7 receptor. These studies show that infection of macrophages with Mycobacterium tuberculosis or M. bovis strain BCG enhances MHC-II release in synergy with ATP. Shed MHC-II was contained in two distinct organelles, exosomes and plasma membrane-derived microvesicles, which were both able to present exogenous antigenic peptide to T hybridoma cells. Furthermore, microvesicles from mycobacterium-infected macrophages were able to directly present M. tuberculosis antigen (Ag) 85B(241-256)-I-Ab complexes that were generated by the processing of M. tuberculosis Ag 85B in infected cells to both M. tuberculosis-specific T hybridoma cells and naïve P25 M. tuberculosis T-cell receptor (TCR)-transgenic T cells. In the presence of prefixed macrophages, exosomes from mycobacterium-infected macrophages provided weak stimulation to M. tuberculosis-specific T hybridoma cells but not naïve P25 T cells. Thus, infection with M. tuberculosis primes macrophages for the increased release of exosomes and microvesicles bearing M. tuberculosis peptide-MHC-II complexes that may generate antimicrobial T-cell responses.

scholarly journals A Direct Role for the CD1b Endogenous Spacer in the Recognition of a Mycobacterium tuberculosis Antigen by T-Cell Receptors

2020 ◽  
Vol 11 ◽  
Author(s):  
Frank Camacho ◽  
Ernesto Moreno ◽  
Luis F. Garcia-Alles ◽  
Glay Chinea Santiago ◽  
Martine Gilleron ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Receptors ◽  
Direct Role ◽  
Cell Receptors ◽  
Tuberculosis Antigen ◽  
Mycobacterium Tuberculosis Antigen

scholarly journals Processing of Mycobacterium tuberculosis Antigen 85B Involves Intraphagosomal Formation of Peptide–Major Histocompatibility Complex II Complexes and Is Inhibited by Live Bacilli that Decrease Phagosome Maturation

2001 ◽  
Vol 194 (10) ◽  
pp. 1421-1432 ◽  
Author(s):  
Lakshmi Ramachandra ◽  
Erika Noss ◽  
W. Henry Boom ◽  
Clifford V. Harding
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Immune Surveillance ◽  
Interferon Γ ◽  
Hybridoma Cells ◽  
Phagosome Maturation ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex

Mycobacterium tuberculosis (MTB) inhibits phagosomal maturation to promote its survival inside macrophages. Control of MTB infection requires CD4 T cell responses and major histocompatibility complex (MHC) class II (MHC-II) processing of MTB antigens (Ags). To investigate phagosomal processing of MTB Ags, phagosomes containing heat-killed (HK) or live MTB were purified from interferon-γ (IFN-γ)–activated macrophages by differential centrifugation and Percoll density gradient subcellular fractionation. Flow organellometry and Western blot analysis showed that MTB phagosomes acquired lysosome-associated membrane protein-1 (LAMP-1), MHC-II, and H2-DM. T hybridoma cells were used to detect MTB Ag 85B(241–256)–I-Ab complexes in isolated phagosomes and other subcellular fractions. These complexes appeared initially (within 20 min) in phagosomes and subsequently (>20 min) on the plasma membrane, but never within late endocytic compartments. Macrophages processed HK MTB more rapidly and efficiently than live MTB; phagosomes containing live MTB expressed fewer Ag 85B(241–256)–I-Ab complexes than phagosomes containing HK MTB. This is the first study of bacterial Ag processing to directly show that peptide–MHC-II complexes are formed within phagosomes and not after export of bacterial Ags from phagosomes to endocytic Ag processing compartments. Live MTB can alter phagosome maturation and decrease MHC-II Ag processing, providing a mechanism for MTB to evade immune surveillance and enhance its survival within the host.

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