| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107
We investigated the roles of nascent and recycling MHC class II molecules (MHC II) in the presentation of two well-defined I-Ed-restricted epitopes that are within distinct regions of the influenza virus hemagglutinin (HA) protein. The site 3 epitope (S3; residues 302–313) lies in the stalk region that unfolds in response to mild acidification, while the site 1 epitope (S1; residues 107–119) is situated in the stable globular domain. In a murine B lymphoma cell line and an I-Ed-transfected fibroblast cell line, presentation from inactivated virus of S3 is inhibited by primaquine, a compound that prevents recycling of cell surface proteins, including MHC II, while S1 presentation is unaffected. In contrast, brefeldin A, an agent that inhibits exit of proteins from the endoplasmic reticulum, selectively inhibited S1 presentation without affecting S3 presentation, suggesting that S1 presentation requires nascent MHC II. The use of agents that perturb endosomal function revealed a requirement for acidification of internalized viral particles for presentation of both epitopes. Notably, all compounds tested had similar effects on presentation of the two epitopes derived from endogenously synthesized HA. Thus, recycling I-Ed molecules appear to be crucial for capturing and presenting an epitope that is revealed in mild acidic conditions following the uptake of virions or the synthesis of Ag, while nascent I-Ed molecules are required for presentation of a second epitope located in a structurally constrained region of the same polypeptide. Viral glycoproteins, such as HA, may have been a major impetus for the evolutionary establishment of this recycling pathway.
This article has been cited by other articles:
|
|
 |
|
  R. Knorr, C. Karacsonyi, and R. Lindner Endocytosis of MHC molecules by distinct membrane rafts J. Cell Sci., May 15, 2009; 122(10): 1584 - 1594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Mi, S. Wanjie, S.-T. Lo, Z. Gan, B. Pickl-Herk, R. J. Ober, and E. S. Ward Targeting the Neonatal Fc Receptor for Antigen Delivery Using Engineered Fc Fragments J. Immunol., December 1, 2008; 181(11): 7550 - 7561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Robila, M. Ostankovitch, M. L. Altrich-VanLith, A. C. Theos, S. Drover, M. S. Marks, N. Restifo, and V. H. Engelhard MHC Class II Presentation of gp100 Epitopes in Melanoma Cells Requires the Function of Conventional Endosomes and Is Influenced by Melanosomes J. Immunol., December 1, 2008; 181(11): 7843 - 7852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Walseng, O. Bakke, and P. A. Roche Major Histocompatibility Complex Class II-Peptide Complexes Internalize Using a Clathrin- and Dynamin-independent Endocytosis Pathway J. Biol. Chem., May 23, 2008; 283(21): 14717 - 14727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mimura, Y. Mimura-Kimura, K. Doores, D. Golgher, B. G. Davis, R. A. Dwek, P. M. Rudd, and T. Elliott Folding of an MHC class II-restricted tumor antigen controls its antigenicity via MHC-guided processing PNAS, April 3, 2007; 104(14): 5983 - 5988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Lefebvre, M. C. Haks, M. O. Carleton, M. Rhodes, G. Sinnathamby, M. C. Simon, L. C. Eisenlohr, L. A. Garrett-Sinha, and D. L. Wiest Enforced Expression of Spi-B Reverses T Lineage Commitment and Blocks {beta}-Selection J. Immunol., May 15, 2005; 174(10): 6184 - 6194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Disbrow, J. A. Hanover, and R. Schlegel Endoplasmic Reticulum-Localized Human Papillomavirus Type 16 E5 Protein Alters Endosomal pH but Not trans-Golgi pH J. Virol., May 1, 2005; 79(9): 5839 - 5846. [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]
|
|
|
|
|
|
J. A. Musson, N. Walker, H. Flick-Smith, E. D. Williamson, and J. H. Robinson Differential Processing of CD4 T-cell Epitopes from the Protective Antigen of Bacillus anthracis J. Biol. Chem., December 26, 2003; 278(52): 52425 - 52431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Moron, P. Rueda, C. Sedlik, and C. Leclerc In Vivo, Dendritic Cells Can Cross-Present Virus-Like Particles Using an Endosome-to-Cytosol Pathway J. Immunol., September 1, 2003; 171(5): 2242 - 2250. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
