| Viral sequestration of antigen subverts cross presentation to CD8 T cells. | |
| | |
MedLine Citation:
|
PMID: 19440337 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Virus-specific CD8(+) T cells (T(CD8+)) are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells (pAPC). Peptide-MHC complexes are produced by two spatially distinct pathways during virus infection. Endogenous antigens synthesized within virus-infected pAPC are presented via the direct-presentation pathway. Many viruses have developed strategies to subvert direct presentation. When direct presentation is blocked, the cross-presentation pathway, in which antigen is transferred from virus-infected cells to uninfected pAPC, is thought to compensate and allow the generation of effector T(CD8+). Direct presentation of vaccinia virus (VACV) antigens driven by late promoters does not occur, as an abortive infection of pAPC prevents production of these late antigens. This lack of direct presentation results in a greatly diminished or ablated T(CD8+) response to late antigens. We demonstrate that late poxvirus antigens do not enter the cross-presentation pathway, even when identical antigens driven by early promoters access this pathway efficiently. The mechanism mediating this novel means of viral modulation of antigen presentation involves the sequestration of late antigens within virus factories. Early antigens and cellular antigens are cross-presented from virus-infected cells, as are late antigens that are targeted to compartments outside of the virus factories. This virus-mediated blockade specifically targets the cross-presentation pathway, since late antigen that is not cross-presented efficiently enters the MHC Class II presentation pathway. These data are the first to describe an evasion mechanism employed by pathogens to prevent entry into the cross-presentation pathway. In the absence of direct presentation, this evasion mechanism leads to a complete ablation of the T(CD8+) response and a potential replicative advantage for the virus. Such mechanisms of viral modulation of antigen presentation must also be taken into account during the rational design of antiviral vaccines. |
| | |
Authors:
|
Eric F Tewalt; Jean M Grant; Erica L Granger; Douglas C Palmer; Neal D Heuss; Dale S Gregerson; Nicholas P Restifo; Christopher C Norbury |
Related Documents
:
|
7596557 - Cytotoxic t lymphocyte activity after intravitreal inoculation of herpes simplex virus ... 8822627 - Impaired generation of anti-akr/gross murine leukemia virus cytotoxic t lymphocytes in ... 16231287 - Virus-induced polyclonal b cell activation improves protective ctl memory via retained ... 17202217 - The level of viral antigen presented by hepatocytes influences cd8 t-cell function. 9094687 - Development of aids in a chimpanzee infected with human immunodeficiency virus type 1. 23244217 - Inflammatory monocytes and the pathogenesis of viral encephalitis. |
Publication Detail:
|
Type: Journal Article Date: 2009-05-29 |
Journal Detail:
|
Title: PLoS pathogens Volume: 5 ISSN: 1553-7374 ISO Abbreviation: PLoS Pathog. Publication Date: 2009 May |
Date Detail:
|
Created Date: 2009-05-14 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101238921 Medline TA: PLoS Pathog Country: United States |
Other Details:
|
Languages: eng Pagination: e1000457 Citation Subset: IM |
Affiliation:
|
Department of Microbiology and Immunology, Pennsylvania State University, Milton S. Hershey College of Medicine, Hershey, Pennsylvania, United States of America. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Analysis of Functional Genomic Signals Using the XOR Gate.
Next Document: Myocardial Overexpression of Mecr, a Gene of Mitochondrial FAS II Leads to Cardiac Dysfunction in Mo...