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5d2n
From Proteopedia
Crystal structure of C25-NLV-HLA-A2 complex
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[B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. [1A02_HUMAN] Involved in the presentation of foreign antigens to the immune system. Publication Abstract from PubMedCytomegalovirus (CMV) is a ubiquitous and persistent human pathogen that is kept in check by CD8(+) cytotoxic T lymphocytes. Individuals expressing the major histocompatibility complex (MHC) class I molecule HLA-A2 produce cytotoxic T lymphocytes bearing T cell receptors (TCRs) that recognize the immunodominant CMV epitope NLVPMVATV (NLV). The NLV-specific T cell repertoire is characterized by a high prevalence of TCRs that are frequently observed in multiple unrelated individuals. These public TCRs feature identical, or nearly identical, complementarity-determining region 3alpha (CDR3alpha) and/or CDR3beta sequences. The TCRs may express public CDR3alpha motifs alone, public CDR3beta motifs alone, or dual public CDR3alphabeta motifs. In addition, the same public CDR3alpha motif may pair with different CDR3beta motifs (and the reverse), giving rise to highly diverse NLV-specific TCR repertoires. To investigate the structural underpinnings of this clonal diversity, we determined crystal structures of two public TCRs (C7 and C25) in complex with NLV.HLA-A2. These TCRs utilize completely different CDR3alpha and CDR3beta motifs that, in addition, can associate with multiple variable alpha and variable beta regions in NLV-specific T cell repertoires. The C7.NLV.HLA-A2 and C25.NLV.HLA-A2 complexes exhibit divergent TCR footprints on peptide-MHC such that C25 is more focused on the central portion of the NLV peptide than is C7. These structures combined with molecular modeling show how the public CDR3alpha motif of C25 may associate with different variable alpha regions and how the public CDR3alpha motif of C7 may pair with different CDR3beta motifs. This interchangeability of TCR V regions and CDR3 motifs permits multiple structural solutions to binding an identical peptide-MHC ligand and thereby the generation of a clonally diverse public T cell response to CMV. Structural Basis for Clonal Diversity of the Public T Cell Response to a Dominant Human Cytomegalovirus Epitope.,Yang X, Gao M, Chen G, Pierce BG, Lu J, Weng NP, Mariuzza RA J Biol Chem. 2015 Nov 27;290(48):29106-19. doi: 10.1074/jbc.M115.691311. Epub, 2015 Oct 1. PMID:26429912[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Mariuzza, R A | Yang, X | Hla-a2 | Immune system | Nlv | Tcr
