ArticleThe Journal of biological chemistry2017
The molecular basis for peptide repertoire selection in the human leucocyte antigen (HLA) C*06:02 molecule.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- HLA-C*06:02-independent, gender-related association of PSORS1C3 and PSORS1C1/CDSN single-nucleotide polymorphisms with risk and severity of psoriasis.Molecular genetics and genomics : MGG · 2018Trial
- Structural evolution of polymorphic class I HLA alleles, designating HLA-C with uncertain assemblies.Computational and structural biotechnology journal · 2026Article
- B Cells Can Trigger the T-Cell-Mediated Autoimmune Response Against Melanocytes in Psoriasis.Cells · 2025Article
- Article
- Differential modulation of mutant CALR and JAK2 V617F-driven oncogenesis by HLA genotype in myeloproliferative neoplasms.Frontiers in immunology · 2024Article
- Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity.Frontiers in immunology · 2024Article
- A Lysine Residue at the C-Terminus of MHC Class I Ligands Correlates with Low C-Terminal Proteasomal Cleavage Probability.Biomolecules · 2023Article
- Autoimmune alleles at the major histocompatibility locus modify melanoma susceptibility.American journal of human genetics · 2023Article
- Article
- ERAP1 Controls the Autoimmune Response against Melanocytes in Psoriasis by Generating the Melanocyte Autoantigen and Regulating Its Amount for HLA-C*06:02 Presentation.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Impact of the 'Mis-Peptidome' on HLA Class I-Mediated Diseases: Contribution of ERAP1 and ERAP2 and Effects on the Immune Response.International journal of molecular sciences · 2020Review
- Designing a novel mRNA vaccine against SARS-CoV-2: An immunoinformatics approach.International journal of biological macromolecules · 2020Article
- HLA-C-restricted viral epitopes are associated with an escape mechanism from KIR2DL2EBioMedicine · 2019Article
- Adaptive and Innate Immunity in Psoriasis and Other Inflammatory Disorders.Frontiers in immunology · 2019Review
- Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages.NPJ vaccines · 2019Article
- Ranking the Contribution of Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphisms to Shaping the HLA-B*27 Peptidome.Molecular & cellular proteomics : MCP · 2018Article
- Predicting Antigen Presentation-What Could We Learn From a Million Peptides?Frontiers in immunology · 2018Review
- Discrimination Between Human Leukocyte Antigen Class I-Bound and Co-Purified HIV-Derived Peptides in Immunopeptidomics Workflows.Frontiers in immunology · 2018Article
- Human Leukocyte Antigen-Class I Alleles and the Autoreactive T Cell Response in Psoriasis Pathogenesis.Frontiers in immunology · 2018Review
- How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins.Frontiers in immunology · 2018Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human leukocyte antigen (HLA)-C*06:02 is identified as the allele associated with the highest risk for the development of the autoimmune skin disease psoriasis. However, the diversity and mode of peptide presentation by the HLA-C*06:02 molecule remains unclear. Here, we describe the endogenous peptide repertoire of ∼3,000 sequences for HLA-C*06:02 that defines the peptide-binding motif for this HLA allomorph. We found that HLA-C*06:02 predominantly presents nonamer peptides with dominant arginine anchors at the P2 and P7 positions and a preference for small hydrophobic residues at the C terminus (PΩ). To determine the structural basis of this selectivity, we determined crystal structures of HLA-C*06:02 in complex with two self-peptides (ARTELYRSL and ARFNDLRFV) and an analogue of a melanocyte autoantigen (ADAMTSL5, VRSRR-abu-LRL) implicated in psoriasis. These structures revealed that HLA-C*06:02 possesses a deep peptide-binding groove comprising two electronegative B- and E-pockets that coincide with the preference for P2 and P7 arginine anchors. The ADAMTSL5 autoantigen possessed a P7-Leu instead of the P7-Arg residue, but nevertheless was accommodated within the HLA-C*06:02 antigen-binding cleft. Collectively, our results provide the structural basis for understanding peptide repertoire selection in HLA-C*06:02.
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