4nt6

HLA-C*0801 Crystal Structure

spinqualitylabelsall models 4nt6, resolution 1.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nt6 is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 4nt7 Resources: FirstGlance, OCA, RCSB, PDBsum Disease [B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation. Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis. Function [1C08_HUMAN] Involved in the presentation of foreign antigens to the immune system. [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMed Cytotoxic T lymphocytes recognizing conserved peptide epitopes are crucial in the protection against influenza A virus (IAV) infection. The CD8 T cell response against the M158-66 (GILGFVFTL) matrix protein epitope is immunodominant when restricted by HLA-A*02, a major histocompatibility complex (MHC) expressed by approximately half of the human population. Herein, we report that the GILGFVFTL peptide is restricted by multiple HLA-C*08 alleles as well. We observed that M158-66 was able to elicit CTL responses in both HLA-A*02 and -C*08 positive individuals; and that GILGFVFTL-specific CTLs in individuals expressing both restriction elements were distinct and not cross-reactive. The crystal structure of GILGFVFTL/HLA-C*08:01 was solved at 1.84A and comparison with the known GILGFVFTL/HLA-A*02:01 structure revealed that the antigen bound both complexes in near-identical conformation, accommodated by binding pockets shaped from shared as well as unique residues. This discovery of degenerate peptide presentation by both HLA-A and HLA-C allelic variants eliciting unique CTL responses to IAV infection contributes fundamental knowledge with important implications for vaccine development strategies. IMPORTANCE: The presentation of influenza A virus peptide to elicit immunity is thought to be narrowly restricted, with a single peptide presented by a specific HLA molecule. In this study, we show that the same influenza A peptide can be more broadly presented by both HLA-A and HLA-C molecules. This discovery may help to explain the differences in immunity to influenza A between individuals and populations, and also aid in the design of vaccines. The immunodominant Influenza A virus M158-66 CTL epitope exhibits degenerate class I MHC restriction in humans.,Choo JA, Liu J, Toh X, Grotenbreg GM, Ren EC J Virol. 2014 Jul 2. pii: JVI.00855-14. PMID:24990997 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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