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==The molecular bases of Delta/Alpha beta T cell-mediated antigen recognition.==
==The molecular bases of Delta/Alpha beta T cell-mediated antigen recognition.==
<StructureSection load='4wo4' size='340' side='right' caption='[[4wo4]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='4wo4' size='340' side='right'caption='[[4wo4]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4wo4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WO4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WO4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4wo4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WO4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=JLS:(15Z)-N-[(2S,3S,4R)-1-(ALPHA-D-GALACTOPYRANOSYLOXY)-3,4-DIHYDROXYOCTADECAN-2-YL]TETRACOS-15-ENAMIDE'>JLS</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wnq|4wnq]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=JLS:(15Z)-N-[(2S,3S,4R)-1-(ALPHA-D-GALACTOPYRANOSYLOXY)-3,4-DIHYDROXYOCTADECAN-2-YL]TETRACOS-15-ENAMIDE'>JLS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wo4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wo4 RCSB], [http://www.ebi.ac.uk/pdbsum/4wo4 PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4wo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wo4 OCA], [https://pdbe.org/4wo4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wo4 RCSB], [https://www.ebi.ac.uk/pdbsum/4wo4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wo4 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref>  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.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> 
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CD1D_HUMAN CD1D_HUMAN]] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:17475845</ref> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.  
[https://www.uniprot.org/uniprot/CD1D_HUMAN CD1D_HUMAN] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:17475845</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
alphabeta and gammadelta T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the alphabeta and gammadelta T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term delta/alphabeta T cells, expressing TCRs comprised of a TCR-delta variable gene (Vdelta1) fused to joining alpha and constant alpha domains, paired with an array of TCR-beta chains. We demonstrate that these cells, which represent approximately 50% of all Vdelta1(+) human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive delta/alphabeta T cells recognized alpha-galactosylceramide (alpha-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as alpha-glucosylceramide, was distinct from type I NKT cells. Thus, delta/alphabetaTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how delta/alphabetaTCRs bind to their targets, with the Vdelta1-encoded region providing a major contribution to delta/alphabetaTCR binding. Our findings highlight how components from alphabeta and gammadeltaTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.
 
The molecular bases of delta/alphabeta T cell-mediated antigen recognition.,Pellicci DG, Uldrich AP, Le Nours J, Ross F, Chabrol E, Eckle SB, de Boer R, Lim RT, McPherson K, Besra G, Howell AR, Moretta L, McCluskey J, Heemskerk MH, Gras S, Rossjohn J, Godfrey DI J Exp Med. 2014 Dec 15;211(13):2599-615. doi: 10.1084/jem.20141764. Epub 2014 Dec, 1. PMID:25452463<ref>PMID:25452463</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wo4" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[CD1|CD1]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Besra, G]]
[[Category: Homo sapiens]]
[[Category: Boer, R de]]
[[Category: Large Structures]]
[[Category: Chabrol, E]]
[[Category: Besra G]]
[[Category: Eckle, S B.G]]
[[Category: Chabrol E]]
[[Category: Godfrey, D I]]
[[Category: Eckle SBG]]
[[Category: Gras, S]]
[[Category: Godfrey DI]]
[[Category: Heemskerk, M H.M]]
[[Category: Gras S]]
[[Category: Howell, A R]]
[[Category: Heemskerk MHM]]
[[Category: Lim, R T]]
[[Category: Howell AR]]
[[Category: McCluskey, J]]
[[Category: Le Nours J]]
[[Category: McPherson, K]]
[[Category: Lim RT]]
[[Category: Moretta, L]]
[[Category: McCluskey J]]
[[Category: Nours, J Le]]
[[Category: McPherson K]]
[[Category: Pellicci, D G]]
[[Category: Moretta L]]
[[Category: Ross, F]]
[[Category: Pellicci DG]]
[[Category: Rossjohn, J]]
[[Category: Ross F]]
[[Category: Uldrich, A P]]
[[Category: Rossjohn J]]
[[Category: Immune system]]
[[Category: Uldrich AP]]
[[Category: Immunity]]
[[Category: De Boer R]]

Latest revision as of 03:54, 28 December 2023

The molecular bases of Delta/Alpha beta T cell-mediated antigen recognition.The molecular bases of Delta/Alpha beta T cell-mediated antigen recognition.

Structural highlights

4wo4 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD1D_HUMAN Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.[1]

Publication Abstract from PubMed

alphabeta and gammadelta T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the alphabeta and gammadelta T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term delta/alphabeta T cells, expressing TCRs comprised of a TCR-delta variable gene (Vdelta1) fused to joining alpha and constant alpha domains, paired with an array of TCR-beta chains. We demonstrate that these cells, which represent approximately 50% of all Vdelta1(+) human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive delta/alphabeta T cells recognized alpha-galactosylceramide (alpha-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as alpha-glucosylceramide, was distinct from type I NKT cells. Thus, delta/alphabetaTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how delta/alphabetaTCRs bind to their targets, with the Vdelta1-encoded region providing a major contribution to delta/alphabetaTCR binding. Our findings highlight how components from alphabeta and gammadeltaTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.

The molecular bases of delta/alphabeta T cell-mediated antigen recognition.,Pellicci DG, Uldrich AP, Le Nours J, Ross F, Chabrol E, Eckle SB, de Boer R, Lim RT, McPherson K, Besra G, Howell AR, Moretta L, McCluskey J, Heemskerk MH, Gras S, Rossjohn J, Godfrey DI J Exp Med. 2014 Dec 15;211(13):2599-615. doi: 10.1084/jem.20141764. Epub 2014 Dec, 1. PMID:25452463[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Chen X, Wang X, Keaton JM, Reddington F, Illarionov PA, Besra GS, Gumperz JE. Distinct endosomal trafficking requirements for presentation of autoantigens and exogenous lipids by human CD1d molecules. J Immunol. 2007 May 15;178(10):6181-90. PMID:17475845
  2. ↑ Pellicci DG, Uldrich AP, Le Nours J, Ross F, Chabrol E, Eckle SB, de Boer R, Lim RT, McPherson K, Besra G, Howell AR, Moretta L, McCluskey J, Heemskerk MH, Gras S, Rossjohn J, Godfrey DI. The molecular bases of delta/alphabeta T cell-mediated antigen recognition. J Exp Med. 2014 Dec 15;211(13):2599-615. doi: 10.1084/jem.20141764. Epub 2014 Dec, 1. PMID:25452463 doi:http://dx.doi.org/10.1084/jem.20141764

4wo4, resolution 2.50Å

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