4i4w

Peptide length determines the outcome of T cell receptor/peptide-MHCI engagement

spinqualitylabelsall models 4i4w, resolution 1.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4i4w is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, GOL, SO4 Gene: HLA-A, HLAA (Homo sapiens), B2M, CDABP0092, HDCMA22P (Homo sapiens) 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 [1A02_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 The alphabeta T-cell receptors (TCRs) expressed at the CD8(+) T-cell surface interact with short peptide fragments (p), bound to major histocompatibility complex class I (MHCI) molecules. The TCR/pMHCI interaction is pivotal in all aspects of CD8(+) T-cell immunity. However, the rules that govern the outcome of TCR/pMHCI engagement are not entirely understood which is a major barrier to understanding the requirements for both effective immunity and vaccination. Here, we have discovered an unexpected feature of the TCR/pMHCI interaction by showing that any given TCR exhibits an explicit preference for a single MHCI-peptide length. Agonists of non-preferred length were extremely rare, suboptimal and often entirely distinct in sequence. Structural analysis indicated that alterations in peptide length have a major impact on antigenic complexity, to which individual TCRs are unable to adapt. This novel finding demonstrates that the outcome of TCR/pMHCI engagement is determined by peptide length in addition to the sequence identity of the MHCI-bound peptide. Accordingly, the effective recognition of pMHCI antigen, which is a prerequisite for successful CD8(+) T-cell immunity and protective vaccination, can only be achieved by "length-matched" antigen-specific CD8(+) T-cell clonotypes. Peptide length determines the outcome of T cell receptor/peptide-MHCI engagement.,Ekeruche-Makinde J, Miles JJ, van den Berg HA, Skowera A, Cole DK, Dolton G, Schauenburg AJ, Tan MP, Pentier JM, Llewellyn-Lacey S, Miles KM, Bulek AM, Clement M, Williams T, Trimby A, Bailey M, Rizkallah P, Rossjohn J, Peakman M, Price DA, Burrows SR, Sewell AK, Wooldridge L Blood. 2012 Dec 18. PMID:23255554 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin

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