| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 147, Issue 12 4054-4059, Copyright © 1991 by American Association of Immunologists
ARTICLES |
DS Collins, ER Unanue and CV Harding
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Reduction of disulfide bonds is a key step in antigen processing both to allow the unfolding of protein antigens, increasing the access of proteolytic processing enzymes, and to expose free Cys residues within linear peptide epitopes recognized by T cells. We show here that reduction and alkylation of Ag (hen egg lysozyme and ribonuclease A) vastly increased their proteolysis (by specific enzymes or lysosomal fractions) and the production of specific immunogenic peptides that bound to class II MHC molecules recognized by T hybridoma cells. We also show that the lysosome is the vesicular compartment that mediates protein disulfide reduction. We coupled [125I]tyrosine to 131I-alpha 2- macroglobulin or [131I] transferrin via a reducible disulfide linker. Removal of [125I]tyrosine from the alpha 2-macroglobulin conjugate was initiated only after 15 to 20 min of uptake by macrophages, suggesting that reduction occurred late in the endocytic pathway. No reduction of transferrin conjugates was seen, indicating that early, recycling endosomes did not contain reducing activity. Subcellular fractionation showed that the disulfide bonds were reduced only in heavy density (lysosome) fractions and remained intact in fractions of light density (endosomes and plasma membrane). These results indicate the importance of lysosomes in the biochemical processing of protein Ag presented to T cells.
This article has been cited by other articles:
|
|
 |
|
  T. R. Dagenais, K. P. Demick, J. D. Bangs, K. T. Forest, D. M. Paulnock, and J. M. Mansfield T-Cell Responses to the Trypanosome Variant Surface Glycoprotein Are Not Limited to Hypervariable Subregions Infect. Immun., January 1, 2009; 77(1): 141 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Breunig, U. Lungwitz, R. Liebl, and A. Goepferich Breaking up the correlation between efficacy and toxicity for nonviral gene delivery PNAS, September 4, 2007; 104(36): 14454 - 14459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Hastings, R. L. Lackman, and P. Cresswell Functional Requirements for the Lysosomal Thiol Reductase GILT in MHC Class II-Restricted Antigen Processing J. Immunol., December 15, 2006; 177(12): 8569 - 8577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Austin, X. Wen, L. Gazzard, C. Nelson, R. H. Scheller, and S. J. Scales Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody-drug conjugates PNAS, December 13, 2005; 102(50): 17987 - 17992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Thai, G. Moine, M. Desmadril, D. Servent, J.-L. Tarride, A. Menez, and M. Leonetti Antigen Stability Controls Antigen Presentation J. Biol. Chem., November 26, 2004; 279(48): 50257 - 50266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. O'Donnell, A. Haque, M. J. Klemsz, M. H. Kaplan, and J. S. Blum Cutting Edge: Induction of the Antigen-Processing Enzyme IFN-{gamma}-Inducible Lysosomal Thiol Reductase in Melanoma Cells Is STAT1-Dependent but CIITA-Independent J. Immunol., July 15, 2004; 173(2): 731 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sinnathamby, M. Maric, P. Cresswell, and L. C. Eisenlohr Differential Requirements for Endosomal Reduction in the Presentation of Two H2-Ed-Restricted Epitopes from Influenza Hemagglutinin J. Immunol., June 1, 2004; 172(11): 6607 - 6614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Brown, J. Stambas, X. Zhan, K. S. Slobod, C. Coleclough, A. Zirkel, S. Surman, S. W. White, P. C. Doherty, and J. L. Hurwitz Clustering of Th Cell Epitopes on Exposed Regions of HIV Envelope Despite Defects in Antibody Activity J. Immunol., October 15, 2003; 171(8): 4140 - 4148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Potolicchio, L. Santambrogio, and J. L. Strominger Molecular Interaction and Enzymatic Activity of Macrophage Migration Inhibitory Factor with Immunorelevant Peptides J. Biol. Chem., August 15, 2003; 278(33): 30889 - 30895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Li, M. A. Haque, and J. S. Blum Role of Disulfide Bonds in Regulating Antigen Processing and Epitope Selection J. Immunol., September 1, 2002; 169(5): 2444 - 2450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Haque, P. Li, S. K. Jackson, H. M. Zarour, J. W. Hawes, U. T. Phan, M. Maric, P. Cresswell, and J. S. Blum Absence of {gamma}-Interferon-inducible Lysosomal Thiol Reductase in Melanomas Disrupts T Cell Recognition of Select Immunodominant Epitopes J. Exp. Med., May 20, 2002; 195(10): 1267 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. M. Lee, D. R. Palmer, K. L. Flanagan, W. H. H. Reece, K. Odhiambo, K. Marsh, M. Pinder, M. B. Gravenor, W. A. Keitel, K. E. Kester, et al. Induction of T Helper Type 1 and 2 Responses to 19-Kilodalton Merozoite Surface Protein 1 in Vaccinated Healthy Volunteers and Adults Naturally Exposed to Malaria Infect. Immun., March 1, 2002; 70(3): 1417 - 1421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Maric, B. Arunachalam, U. T. Phan, C. Dong, W. S. Garrett, K. S. Cannon, C. Alfonso, L. Karlsson, R. A. Flavell, and P. Cresswell Defective Antigen Processing in GILT-Free Mice Science, November 9, 2001; 294(5545): 1361 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Haque, J. W. Hawes, and J. S. Blum Cysteinylation of MHC Class II Ligands: Peptide Endocytosis and Reduction Within APC Influences T Cell Recognition J. Immunol., April 1, 2001; 166(7): 4543 - 4551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gugasyan, C. Velazquez, I. Vidavsky, B. M. Deck, K. van der Drift, M. L. Gross, and E. R. Unanue Independent Selection by I-Ak Molecules of Two Epitopes Found in Tandem in an Extended Polypeptide Antigen J. Immunol., September 15, 2000; 165(6): 3206 - 3213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. J. Huby, R. J. Dearman, and I. Kimber Why Are Some Proteins Allergens? Toxicol. Sci., June 1, 2000; 55(2): 235 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-K. Kang, J. A. Mikszta23, H. Deng, E. E. Sercarz, P. E. Jensen, and B. S. Kim Processing and Reactivity of T Cell Epitopes Containing Two Cysteine Residues from Hen Egg-White Lysozyme (HEL74-90) J. Immunol., February 15, 2000; 164(4): 1775 - 1782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Arunachalam, U. T. Phan, H. J. Geuze, and P. Cresswell Enzymatic reduction of disulfide bonds in lysosomes: Characterization of a Gamma-interferon-inducible lysosomal thiol reductase (GILT) PNAS, January 18, 2000; 97(2): 745 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Unanue Chemical Features of Peptide Selection by the Class II Histocompatibility Molecules Am. J. Pathol., March 1, 1999; 154(3): 651 - 664. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Lewis2, C. B. Hartmann, and K. L. McCoy Gallium Arsenide Modulates Proteolytic Cathepsin Activities and Antigen Processing by Macrophages J. Immunol., September 1, 1998; 161(5): 2151 - 2157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sone, K. Morikubo, M. Miyahara, N. Komiyama, K. Shimizu, H. Tsunoo, and K. Kino T Cell Epitopes in Japanese Cedar (Cryptomeria japonica) Pollen Allergens: Choice of Major T Cell Epitopes in Cry j 1 and Cry j 2 Toward Design of the Peptide-Based Immunotherapeutics for the Management of Japanese Cedar Pollinosis J. Immunol., July 1, 1998; 161(1): 448 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Arunachalam, M. Pan, and P. Cresswell Intracellular Formation and Cell Surface Expression of a Complex of an Intact Lysosomal Protein and MHC Class II Molecules J. Immunol., June 15, 1998; 160(12): 5797 - 5806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Peterson, L. A. Herzenberg, K. Vasquez, and C. Waltenbaugh Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns PNAS, March 17, 1998; 95(6): 3071 - 3076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. So, H.-O Ito, T. Koga, S. Watanabe, T. Ueda, and T. Imoto Depression of T-cell Epitope Generation by Stabilizing Hen Lysozyme J. Biol. Chem., December 19, 1997; 272(51): 32136 - 32140. [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]
|
|
|
|
 |
|
 C.A. Nelson, C.V. Harding, and E.R. Unanue Biochemical Anatomy of Antigen Processing Cold Spring Harb Symp Quant Biol, January 1, 1992; 57(0): 557 - 563. [Abstract] [PDF]
|
|
|
|
|
|
U. T. Phan, B. Arunachalam, and P. Cresswell Gamma-Interferon-inducible Lysosomal Thiol Reductase (GILT). MATURATION, ACTIVITY, AND MECHANISM OF ACTION J. Biol. Chem., August 18, 2000; 275(34): 25907 - 25914. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
