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3gsq
From Proteopedia
Crystal structure of the binary complex between HLA-A2 and HCMV NLV-M5S peptide variant
Structural highlights
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.[1] 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.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedProtective T cell responses elicited along chronic human CMV (HCMV) infections are sometimes dominated by CD8 T cell clones bearing highly related or identical public TCR in unrelated individuals. To understand the principles that guide emergence of these public T cell responses, we have performed structural, biophysical, and functional analyses of an immunodominant public TCR (RA14) directed against a major HLA-A*0201-restricted HCMV Ag (pp65(495-503)) and selected in vivo from a diverse repertoire after chronic stimulations. Unlike the two immunodominant public TCRs crystallized so far, which focused on one peptide hotspot, the HCMV-specific RA14 TCR interacts with the full array of available peptide residues. The conservation of some peptide-MHC complex-contacting amino acids by lower-affinity TCRs suggests a shared TCR-peptide-MHC complex docking mode and supports an Ag-driven selection of optimal TCRs. Therefore, the emergence of a public TCR of an oligoclonal Ag-specific response after repeated viral stimulations is based on a receptor displaying a high structural complementarity with the entire peptide and focusing on three peptide hotspots. This highlights key parameters underlying the selection of a protective T cell response against HCMV infection, which remains a major health issue in patients undergoing bone marrow transplantation. Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope.,Gras S, Saulquin X, Reiser JB, Debeaupuis E, Echasserieau K, Kissenpfennig A, Legoux F, Chouquet A, Le Gorrec M, Machillot P, Neveu B, Thielens N, Malissen B, Bonneville M, Housset D J Immunol. 2009 Jul 1;183(1):430-7. PMID:19542454[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Bonneville, M | Chouquet, A | Debeaupuis, E | Echasserieau, K | Gorrec, M Le | Gras, S | Housset, D | Kissenpfennig, A | Legoux, F | Machillot, P | Malissen, B | Neveu, B | Reiser, J B | Saulquin, X | Thielens, N | Hla | Host-virus interaction | Human cytomegalovirus | Immune response | Immune system | Immunodominance | Immunoglobulin domain | Membrane | Mhc i | Polymorphism | Pp65 | Public response | Restrained response
