| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 151, Issue 8 3988-3998, Copyright © 1993 by American Association of Immunologists
ARTICLES |
CV Harding and HJ Geuze
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Exogenous protein Ag are processed within endocytic compartments to produce peptides that bind to class II MHC (MHC-II) molecules for presentation to T cells. We have now identified a subcellular compartment in which immunogenic peptides bind to MHC-II as a subset of high density lysosomes. Immunoelectron microscopy of whole cells and dense Percoll gradient subcellular fractions showed early tubulovesicular lysosomes with high levels of MHC-II. Typical mature lysosomes contained less MHC-II. Pulse-chase biosynthetic labeling of macrophages followed by immunoprecipitation of MHC-II from dense lysosomal fractions showed that MHC-II molecules targeted efficiently to lysosomes after biosynthesis. Moreover, lysosomal MHC-II molecules were rapidly loaded with immunogenic peptide (as detected by T cells) soon after exposure of macrophages to Ag and before similar expression of peptide-MHC-II complexes on the plasma membrane; this loading was blocked at 18 degrees C. We propose that nascent MHC-II molecules target to early tubulovesicular lysosomes and bind immunogenic peptides therein; the resulting peptide-MHC-II complexes are then transported to the plasma membrane.
This article has been cited by other articles:
|
|
 |
|
  M. Torres, L. Ramachandra, R. E. Rojas, K. Bobadilla, J. Thomas, D. H. Canaday, C. V. Harding, and W. H. Boom Role of Phagosomes and Major Histocompatibility Complex Class II (MHC-II) Compartment in MHC-II Antigen Processing of Mycobacterium tuberculosis in Human Macrophages Infect. Immun., March 1, 2006; 74(3): 1621 - 1630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Neild, T. Murata, and C. R. Roy Processing and Major Histocompatibility Complex Class II Presentation of Legionella pneumophila Antigens by Infected Macrophages Infect. Immun., April 1, 2005; 73(4): 2336 - 2343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ramachandra, J. L. Smialek, S. S. Shank, M. Convery, W. H. Boom, and C. V. Harding Phagosomal Processing of Mycobacterium tuberculosis Antigen 85B Is Modulated Independently of Mycobacterial Viability and Phagosome Maturation Infect. Immun., February 1, 2005; 73(2): 1097 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Brewer, K. G. J. Pollock, L. Tetley, and D. G. Russell Vesicle Size Influences the Trafficking, Processing, and Presentation of Antigens in Lipid Vesicles J. Immunol., November 15, 2004; 173(10): 6143 - 6150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, K. Siemasko, M. R. Clark, and W. Song Cooperative interaction of Ig{alpha} and Ig{beta} of the BCR regulates the kinetics and specificity of antigen targeting Int. Immunol., October 1, 2002; 14(10): 1179 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ramachandra, E. Noss, W. H. Boom, and C. V. Harding 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 J. Exp. Med., November 12, 2001; 194(10): 1421 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Mukherjee, A. Dani, S. Bhatia, N. Singh, A. Y. Rudensky, A. George, V. Bal, S. Mayor, and S. Rath Efficient Presentation of Both Cytosolic and Endogenous Transmembrane Protein Antigens on MHC Class II Is Dependent on Cytoplasmic Proteolysis J. Immunol., September 1, 2001; 167(5): 2632 - 2641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Baron, G Raposo, S. Scholl, H Bausinger, D Tenza, A Bohbot, P Pouillart, B Goud, D Hanau, and J Salamero Modulation of MHC class II transport and lysosome distribution by macrophage-colony stimulating factor in human dendritic cells derived from monocytes J. Cell Sci., January 3, 2001; 114(5): 999 - 1010. [Abstract] [PDF]
|
|
|
|
|
|
K. Denzer, M. van Eijk, M. J. Kleijmeer, E. Jakobson, C. de Groot, and H. J. Geuze Follicular Dendritic Cells Carry MHC Class II-Expressing Microvesicles at Their Surface J. Immunol., August 1, 2000; 165(3): 1259 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. DELL’ANGELICA, C. MULLINS, S. CAPLAN, and J. S. BONIFACINO Lysosome-related organelles FASEB J, July 1, 2000; 14(10): 1265 - 1278. [Abstract] [Full Text]
|
|
|
|
|
|
L. Ramachandra and C. V. Harding Phagosomes Acquire Nascent and Recycling Class II MHC Molecules but Primarily Use Nascent Molecules in Phagocytic Antigen Processing J. Immunol., May 15, 2000; 164(10): 5103 - 5112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Cheng, C. R. Steele, L. Gu, W. Song, and S. K. Pierce MHC Class II Antigen Processing in B Cells: Accelerated Intracellular Targeting of Antigens J. Immunol., June 15, 1999; 162(12): 7171 - 7180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Brown, C. Li, P. C. Cheng, and W. Song Trafficking of the Igalpha /Igbeta Heterodimer with Membrane Ig and Bound Antigen to the Major Histocompatibility Complex Class II Peptide-loading Compartment J. Biol. Chem., April 16, 1999; 274(16): 11439 - 11446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ramachandra, R. Song, and C. V. Harding Phagosomes Are Fully Competent Antigen-Processing Organelles That Mediate the Formation of Peptide:Class II MHC Complexes J. Immunol., March 15, 1999; 162(6): 3263 - 3272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Knolle, T. Germann, U. Treichel, A. Uhrig, E. Schmitt, S. Hegenbarth, A. W. Lohse, and G. Gerken Endotoxin Down-Regulates T Cell Activation by Antigen-Presenting Liver Sinusoidal Endothelial Cells J. Immunol., February 1, 1999; 162(3): 1401 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Castellino, F. Zappacosta, J. E. Coligan, and R. N. Germain Large Protein Fragments as Substrates for Endocytic Antigen Capture by MHC Class II Molecules J. Immunol., October 15, 1998; 161(8): 4048 - 4057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ghumman, E. M. Bertram, and T. H. Watts Chemical Chaperones Enhance Superantigen and Conventional Antigen Presentation by HLA-DM-Deficient as well as HLA-DM-Sufficient Antigen-Presenting Cells and Enhance IgG2a Production In Vivo J. Immunol., October 1, 1998; 161(7): 3262 - 3270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Escola, M. J. Kleijmeer, W. Stoorvogel, J. M. Griffith, O. Yoshie, and H. J. Geuze Selective Enrichment of Tetraspan Proteins on the Internal Vesicles of Multivesicular Endosomes and on Exosomes Secreted by Human B-lymphocytes J. Biol. Chem., August 7, 1998; 273(32): 20121 - 20127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zhong, C. R. e Sousa, and R. N. Germain Production, specificity, and functionality of monoclonal antibodies to specific peptide-major histocompatibility complex class II complexes formed by processing of exogenous protein PNAS, December 9, 1997; 94(25): 13856 - 13861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Kleijmeer, S. Morkowski, J. M. Griffith, A. Y. Rudensky, and H. J. Geuze Major Histocompatibility Complex Class II Compartments in Human and Mouse B Lymphoblasts Represent Conventional Endocytic Compartments J. Cell Biol., November 3, 1997; 139(3): 639 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Ruff, F. G. Guarnieri, K. Staveley-O'Carroll, R. F. Siliciano, and J. T. August The Enhanced Immune Response to the HIV gp160/LAMP Chimeric Gene Product Targeted to the Lysosome Membrane Protein Trafficking Pathway J. Biol. Chem., March 28, 1997; 272(13): 8671 - 8678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhong, P. Romagnoli, and R. N. Germain Related Leucine-based Cytoplasmic Targeting Signals in Invariant Chain and Major Histocompatibility Complex Class II Molecules Control Endocytic Presentation of Distinct Determinants in a Single Protein J. Exp. Med., February 3, 1997; 185(3): 429 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tjelle, A Brech, L. Juvet, G Griffiths, and T Berg Isolation and characterization of early endosomes, late endosomes and terminal lysosomes: their role in protein degradation J. Cell Sci., January 12, 1996; 109(12): 2905 - 2914. [Abstract] [PDF]
|
|
|
|
|
|
J. Escola, J. Grivel, P Chavrier, and J. Gorvel Different endocytic compartments are involved in the tight association of class II molecules with processed hen egg lysozyme and ribonuclease A in B cells J. Cell Sci., January 6, 1995; 108(6): 2337 - 2345. [Abstract] [PDF]
|
|
|
|
 |
|
 F Sanderson, M. Kleijmeer, A Kelly, D Verwoerd, A Tulp, J. Neefjes, H. Geuze, and J Trowsdale Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments Science, December 2, 1994; 266(5190): 1566 - 1569. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
