1zhl
Crystal structure of HLA-B*3508 presenting 13-mer EBV antigen LPEPLPQGQLTAY
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OverviewOverview
Although HLA class I alleles can bind epitopes up to 14 amino acids in, length, little is known about the immunogenicity or the responding T-cell, repertoire against such determinants. Here, we describe an, HLA-B*3508-restricted cytotoxic T lymphocyte response to a 13-mer viral, epitope (LPEPLPQGQLTAY). The rigid, centrally bulged epitope generated a, biased T-cell response. Only the N-terminal face of the peptide bulge was, critical for recognition by the dominant clonotype SB27. The SB27 public, T-cell receptor (TcR) associated slowly onto the complex between the, bulged peptide and the major histocompatibility complex, suggesting, significant remodeling upon engagement. The broad antigen-binding cleft of, HLA-B*3508 represents a critical feature for engagement of the public TcR, as the narrower binding cleft of HLA-B*3501(LPEPLPQGQLTAY), which differs, from HLA-B*3508 by a single amino acid polymorphism (Arg156 --> Leu), interacted poorly with the dominant TcR. Biased TcR usage in this, cytotoxic T lymphocyte response appears to reflect a dominant role of the, prominent peptide x major histocompatibility complex class I surface.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]
About this StructureAbout this Structure
1ZHL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance., Tynan FE, Borg NA, Miles JJ, Beddoe T, El-Hassen D, Silins SL, van Zuylen WJ, Purcell AW, Kjer-Nielsen L, McCluskey J, Burrows SR, Rossjohn J, J Biol Chem. 2005 Jun 24;280(25):23900-9. Epub 2005 Apr 22. PMID:15849183
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