PMID- 22927436 OWN - NLM STAT- MEDLINE DCOM- 20121231 LR - 20231213 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 287 IP - 42 DP - 2012 Oct 12 TI - A viral, transporter associated with antigen processing (TAP)-independent, high affinity ligand with alternative interactions endogenously presented by the nonclassical human leukocyte antigen E class I molecule. PG - 34895-34903 LID - S0021-9258(20)62641-2 [pii] LID - 10.1074/jbc.M112.362293 [doi] AB - The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8(+) lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule. 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 AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. FAU - Abia, David AU - Abia D AD - Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas (CSIC)/Universidad Autonoma de Madrid, 28049 Madrid, Spain. FAU - Barnea, Eilon AU - Barnea E AD - Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. FAU - Beer, Ilan AU - Beer I AD - IBM Haifa Research Lab, Haifa 31905, Israel. FAU - Garcia, Ruth AU - Garcia R AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. FAU - Lasala, Fatima AU - Lasala F AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. FAU - Jimenez, Mercedes AU - Jimenez M AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. FAU - Mir, Carmen AU - Mir C AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. FAU - Morreale, Antonio AU - Morreale A AD - Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas (CSIC)/Universidad Autonoma de Madrid, 28049 Madrid, Spain. FAU - Admon, Arie AU - Admon A AD - Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. FAU - Lopez, Daniel AU - Lopez D AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. Electronic address: dlopez@isciii.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120827 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Antigens, Viral) RN - 0 (D8L protein, vaccinia virus) RN - 0 (HLA-C Antigens) RN - 0 (HLA-Cw1 antigen) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Membrane Proteins) RN - 0 (Peptides) RN - 0 (Viral Structural Proteins) RN - 0 (transporter associated with antigen processing (TAP)) SB - IM MH - ATP-Binding Cassette Transporters/genetics/*immunology/metabolism MH - Amino Acid Motifs MH - *Antigen Presentation MH - Antigens, Viral/genetics/*immunology/metabolism MH - CD8-Positive T-Lymphocytes/*immunology/metabolism MH - Cell Line MH - HLA-C Antigens/genetics/immunology/metabolism MH - Histocompatibility Antigens Class I/genetics/*immunology/metabolism MH - Humans MH - Membrane Proteins/genetics/*immunology/metabolism MH - Peptides/genetics/immunology/metabolism MH - Vaccinia/genetics/*immunology/metabolism MH - Vaccinia virus/genetics/*immunology/metabolism MH - Viral Structural Proteins/genetics/*immunology/metabolism MH - HLA-E Antigens PMC - PMC3471699 EDAT- 2012/08/29 06:00 MHDA- 2013/01/01 06:00 PMCR- 2013/10/12 CRDT- 2012/08/29 06:00 PHST- 2012/08/29 06:00 [entrez] PHST- 2012/08/29 06:00 [pubmed] PHST- 2013/01/01 06:00 [medline] PHST- 2013/10/12 00:00 [pmc-release] AID - S0021-9258(20)62641-2 [pii] AID - M112.362293 [pii] AID - 10.1074/jbc.M112.362293 [doi] PST - ppublish SO - J Biol Chem. 2012 Oct 12;287(42):34895-34903. doi: 10.1074/jbc.M112.362293. Epub 2012 Aug 27.