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Identification and Structure of an MHC Class I-Encoded Protein with the Potential to Present N -Myristoylated 4-mer Peptides to T Cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Jun 15; Vol. 202 (12), pp. 3349-3358. Date of Electronic Publication: 2019 May 01. - Publication Year :
- 2019
-
Abstract
- Similar to host proteins, N -myristoylation occurs for viral proteins to dictate their pathological function. However, this lipid-modifying reaction creates a novel class of "lipopeptide" Ags targeted by host CTLs. The primate MHC class I-encoded protein, Mamu-B*098, was previously shown to bind N -myristoylated 5-mer peptides. Nevertheless, T cells exist that recognize even shorter lipopeptides, and much remains to be elucidated concerning the molecular mechanisms of lipopeptide presentation. We, in this study, demonstrate that the MHC class I allele, Mamu-B*05104, binds the N -myristoylated 4-mer peptide (C14-Gly-Gly-Ala-Ile) derived from the viral Nef protein for its presentation to CTLs. A phylogenetic tree analysis indicates that these classical MHC class I alleles are not closely associated; however, the high-resolution x-ray crystallographic analyses indicate that both molecules share lipid-binding structures defined by the exceptionally large, hydrophobic B pocket to accommodate the acylated glycine (G1) as an anchor. The C-terminal isoleucine (I4) of C14-Gly-Gly-Ala-Ile anchors at the F pocket, which is distinct from that of Mamu-B*098 and is virtually identical to that of the peptide-presenting MHC class I molecule, HLA-B51. The two central amino acid residues (G2 and A3) are only exposed externally for recognition by T cells, and the methyl side chain on A3 constitutes a major T cell epitope, underscoring that the epitopic diversity is highly limited for lipopeptides as compared with that for MHC class I-presented long peptides. These structural features suggest that lipopeptide-presenting MHC class I alleles comprise a distinct MHC class I subset that mediates an alternative pathway for CTL activation.<br /> (Copyright © 2019 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Antigen Presentation
Autoantigens chemistry
Autoantigens immunology
Crystallography, X-Ray
Epitopes, T-Lymphocyte immunology
Gene Products, nef chemistry
Gene Products, nef immunology
Histocompatibility Antigens Class I genetics
Humans
Lipopeptides chemistry
Lipopeptides immunology
Lymphocyte Activation
Myristic Acid chemistry
Peptides chemistry
Peptides immunology
Phylogeny
Primates
Autoantigens metabolism
Epitopes, T-Lymphocyte metabolism
Gene Products, nef metabolism
Histocompatibility Antigens Class I metabolism
Lipopeptides metabolism
Peptides metabolism
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 202
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 31043477
- Full Text :
- https://doi.org/10.4049/jimmunol.1900087