6c61: Difference between revisions
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==MHC-independent T-cell receptor B12A== | |||
<StructureSection load='6c61' size='340' side='right'caption='[[6c61]], [[Resolution|resolution]] 2.43Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6c61]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C61 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6C61 FirstGlance]. <br> | |||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6c61 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c61 OCA], [http://pdbe.org/6c61 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c61 RCSB], [http://www.ebi.ac.uk/pdbsum/6c61 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c61 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
During normal T cell development in the thymus, alphabeta TCRs signal immature thymocytes to differentiate into mature T cells by binding to peptide-MHC ligands together with CD4/CD8 coreceptors. Conversely, in MHC and CD4/CD8 coreceptor-deficient mice, the thymus generates mature T cells expressing MHC-independent TCRs that recognize native conformational epitopes rather than linear antigenic-peptides presented by MHC. To date, no structural information of MHC-independent TCRs is available, and their structural recognition of non-MHC ligand remains unknown. To our knowledge in this study, we determined the first structures of two murine MHC-independent TCRs (A11 and B12A) that bind with high nanomolar affinities to mouse adhesion receptor CD155. Solution binding demonstrated the Valphabeta-domain is responsible for MHC-independent B12A recognition of its ligand. Analysis of A11 and B12A sequences against various MHC-restricted and -independent TCR sequence repertoires showed that individual V-genes of A11 and B12A did not exhibit preference against MHC-restriction. Likewise, CDR3 alone did not discriminate against MHC binding, suggesting VDJ recombination together with Valpha/Vbeta pairing determine their MHC-independent specificity for CD155. The structures of A11 and B12A TCR are nearly identical to those of MHC-restricted TCR, including the conformations of CDR1 and 2. Mutational analysis, together with negative-staining electron microscopy images, showed that the CDR regions of A11 and B12A recognized epitopes on D1 domain of CD155, a region also involved in CD155 binding to poliovirus and Tactile in human. Taken together, MHC-independent TCRs adopt canonical TCR structures to recognize native Ags, highlighting the importance of thymic selection in determining TCR ligand specificity. | |||
Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155.,Lu J, Van Laethem F, Saba I, Chu J, Tikhonova AN, Bhattacharya A, Singer A, Sun PD J Immunol. 2020 Jun 15;204(12):3351-3359. doi: 10.4049/jimmunol.1901084. Epub, 2020 Apr 22. PMID:32321756<ref>PMID:32321756</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6c61" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Lk3 transgenic mice]] | |||
[[Category: Lu, J]] | |||
[[Category: Sun, P]] | |||
[[Category: Immune system]] | |||
[[Category: Mhc-independent t cell receptor]] | |||
Latest revision as of 12:53, 12 August 2020
MHC-independent T-cell receptor B12AMHC-independent T-cell receptor B12A
Structural highlights
Publication Abstract from PubMedDuring normal T cell development in the thymus, alphabeta TCRs signal immature thymocytes to differentiate into mature T cells by binding to peptide-MHC ligands together with CD4/CD8 coreceptors. Conversely, in MHC and CD4/CD8 coreceptor-deficient mice, the thymus generates mature T cells expressing MHC-independent TCRs that recognize native conformational epitopes rather than linear antigenic-peptides presented by MHC. To date, no structural information of MHC-independent TCRs is available, and their structural recognition of non-MHC ligand remains unknown. To our knowledge in this study, we determined the first structures of two murine MHC-independent TCRs (A11 and B12A) that bind with high nanomolar affinities to mouse adhesion receptor CD155. Solution binding demonstrated the Valphabeta-domain is responsible for MHC-independent B12A recognition of its ligand. Analysis of A11 and B12A sequences against various MHC-restricted and -independent TCR sequence repertoires showed that individual V-genes of A11 and B12A did not exhibit preference against MHC-restriction. Likewise, CDR3 alone did not discriminate against MHC binding, suggesting VDJ recombination together with Valpha/Vbeta pairing determine their MHC-independent specificity for CD155. The structures of A11 and B12A TCR are nearly identical to those of MHC-restricted TCR, including the conformations of CDR1 and 2. Mutational analysis, together with negative-staining electron microscopy images, showed that the CDR regions of A11 and B12A recognized epitopes on D1 domain of CD155, a region also involved in CD155 binding to poliovirus and Tactile in human. Taken together, MHC-independent TCRs adopt canonical TCR structures to recognize native Ags, highlighting the importance of thymic selection in determining TCR ligand specificity. Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155.,Lu J, Van Laethem F, Saba I, Chu J, Tikhonova AN, Bhattacharya A, Singer A, Sun PD J Immunol. 2020 Jun 15;204(12):3351-3359. doi: 10.4049/jimmunol.1901084. Epub, 2020 Apr 22. PMID:32321756[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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