PMID- 22031944 OWN - NLM STAT- MEDLINE DCOM- 20120214 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 86 IP - 1 DP - 2012 Jan TI - Multiple viral ligands naturally presented by different class I molecules in transporter antigen processing-deficient vaccinia virus-infected cells. PG - 527-41 LID - 10.1128/JVI.05737-11 [doi] AB - 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 virus-encoded 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. FAU - Lorente, Elena AU - Lorente E AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. FAU - Infantes, Susana AU - Infantes S FAU - Barnea, Eilon AU - Barnea E FAU - Beer, Ilan AU - Beer I FAU - Garcia, Ruth AU - Garcia R FAU - Lasala, Fatima AU - Lasala F FAU - Jimenez, Mercedes AU - Jimenez M FAU - Vilches, Carlos AU - Vilches C FAU - Lemonnier, Francois A AU - Lemonnier FA FAU - Admon, Arie AU - Admon A FAU - Lopez, Daniel AU - Lopez D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111026 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Ligands) RN - 0 (transporter associated with antigen processing (TAP)) SB - IM MH - ATP-Binding Cassette Transporters/genetics/*immunology MH - Animals MH - Antigen Presentation MH - Antigen-Presenting Cells/immunology/virology MH - CD8-Positive T-Lymphocytes/immunology/virology MH - Cell Line MH - Histocompatibility Antigens Class I/genetics/*immunology MH - Humans MH - Ligands MH - Mice MH - Mice, Knockout MH - Vaccinia/genetics/*immunology/virology MH - Vaccinia virus/genetics/*immunology PMC - PMC3255926 EDAT- 2011/10/28 06:00 MHDA- 2012/02/15 06:00 PMCR- 2012/07/01 CRDT- 2011/10/28 06:00 PHST- 2011/10/28 06:00 [entrez] PHST- 2011/10/28 06:00 [pubmed] PHST- 2012/02/15 06:00 [medline] PHST- 2012/07/01 00:00 [pmc-release] AID - JVI.05737-11 [pii] AID - 5737-11 [pii] AID - 10.1128/JVI.05737-11 [doi] PST - ppublish SO - J Virol. 2012 Jan;86(1):527-41. doi: 10.1128/JVI.05737-11. Epub 2011 Oct 26.