Multiple viral ligands naturally presented by different class I molecules in transporter antigen processing-deficient vaccinia virus-infected cells
Entity
UAM. Departamento de MedicinaPublisher
American Society for MicrobiologyDate
2012-01-01Citation
10.1128/JVI.05737-11
Journal of Virology 86.1 (2012): 527-541
ISSN
0022-538X (print); 1098-5514 (online)DOI
10.1128/JVI.05737-11Funded by
This work was supported by grants to D.L. from the Programa Ramón y Cajal, Ministerio de Ciencia e Innovación and the FIPSE Foundation and to A.A. from the ISF 9916/05. The funders had no role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicting financial interestsEditor's Version
http://dx.doi.org/10.1128/JVI.05737-11Subjects
Animals; Antigen-presenting cells; Histocompatibility antigens class I; MedicinaRights
© 2014, American Society for MicrobiologyAbstract
The transporter associated with antigen processing (TAP) delivers the viral proteolytic products generated by the proteasome in
the cytosol to the endoplasmic reticulum lumen that are subsequently recognized by cytotoxic T lymphocytes (CTLs). However,
several viral epitopes have been identified in TAP-deficient models. Using mass spectrometry to analyze complex human leukocyte
antigen (HLA)-bound peptide pools isolated from large numbers of TAP-deficient vaccinia virus-infected cells, we identified
11 ligands naturally presented by four different HLA-A, HLA-B, and HLA-C class I molecules. Two of these ligands were presented
by two different HLA class I alleles, and, as a result, 13 different HLA-peptide complexes were formed simultaneously in
the same vaccinia virus-infected cells. In addition to the high-affinity ligands, one low-affinity peptide restricted by each of the
HLA-A, HLA-B, and HLA-C class I molecules was identified. Both high- and low-affinity ligands generated long-term memory
CTL responses to vaccinia virus in an HLA-A2-transgenic mouse model. The processing and presentation of two vaccinia virusencoded
HLA-A2-restricted antigens took place via proteasomal and nonproteasomal pathways, which were blocked in infected
cells with chemical inhibitors specific for different subsets of metalloproteinases. These data have implications for the study of
the effectiveness of early empirical vaccination with cowpox virus against smallpox disease
Files in this item
Google Scholar:Lorente, Elena
-
Infantes, Susana
-
Barnea, Eilon
-
Beer, Ilan
-
García, Ruth Cabrera
-
Lasala, Fátima
-
Jiménez, Mercedes
-
Vilches Ruiz, Blas Carlos
-
Lemonnier, François A.
-
Admon, Arie
-
López, Daniel
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.
-
Characterization of Vaccinia virus alternative antigen transport and processing pathways for their presentation to cytotoxic CD8+ T lymphocytes
Gamarra Carrasco, David
2017-09-21 -
Comparative studies of antigen expression and interferon production during infection with African swine fever virus isolates of different pathogenicity
González Juarrero, Mercedes
1990-06-29