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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.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2012 Oct 12; Vol. 287 (42), pp. 34895-34903. Date of Electronic Publication: 2012 Aug 27. - Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- ATP-Binding Cassette Transporters genetics
ATP-Binding Cassette Transporters metabolism
Amino Acid Motifs
Antigens, Viral genetics
Antigens, Viral metabolism
CD8-Positive T-Lymphocytes metabolism
Cell Line
HLA-C Antigens genetics
HLA-C Antigens immunology
HLA-C Antigens metabolism
Histocompatibility Antigens Class I genetics
Histocompatibility Antigens Class I metabolism
Humans
Membrane Proteins genetics
Membrane Proteins metabolism
Peptides genetics
Peptides immunology
Peptides metabolism
Vaccinia genetics
Vaccinia metabolism
Vaccinia virus genetics
Vaccinia virus metabolism
Viral Structural Proteins genetics
Viral Structural Proteins metabolism
HLA-E Antigens
ATP-Binding Cassette Transporters immunology
Antigen Presentation
Antigens, Viral immunology
CD8-Positive T-Lymphocytes immunology
Histocompatibility Antigens Class I immunology
Membrane Proteins immunology
Vaccinia immunology
Vaccinia virus immunology
Viral Structural Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 287
- Issue :
- 42
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22927436
- Full Text :
- https://doi.org/10.1074/jbc.M112.362293