T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Autoantigens/*immunology ; Complementarity Determining Regions/*immunology ; Diabetes Mellitus, Type 1/*immunology ; Receptors, Antigen, T-Cell, alpha-beta/*immunology ; V(D)J Recombination/*immunology; Adult ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cell Separation/methods ; Complementarity Determining Regions/genetics ; Complementarity Determining Regions/metabolism ; Diabetes Mellitus, Type 1/genetics ; Female ; Flow Cytometry/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, alpha-beta/metabolism ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Thymus Gland/cytology ; V(D)J Recombination/genetics ; Young Adult
    • Abstract:
      Defects in T cell receptor (TCR) repertoire are proposed to predispose to autoimmunity. Here we show, by analyzing >2 × 10 8 TCRB sequences of circulating naive, central memory, regulatory and stem cell-like memory CD4 + T cell subsets from patients with type 1 diabetes and healthy donors, that patients have shorter TCRB complementarity-determining region 3s (CDR3), in all cell subsets, introduced by increased deletions/reduced insertions during VDJ rearrangement. High frequency of short CDR3s is also observed in unproductive TCRB sequences, which are not subjected to thymic culling, suggesting that the shorter CDR3s arise independently of positive/negative selection. Moreover, TCRB CDR3 clonotypes expressed by autoantigen-specific CD4 + T cells are shorter compared with anti-viral T cells, and with those from healthy donors. Thus, early events in thymic T cell development and repertoire generation are abnormal in type 1 diabetes, which suggest that short CDR3s increase the potential for self-recognition, conferring heightened risk of autoimmune disease.
    • References:
      JCI Insight. 2016 Dec 8;1(20):e88242. (PMID: 27942583)
      Proc Natl Acad Sci U S A. 2009 May 19;106(20):8320-5. (PMID: 19359477)
      Nat Genet. 2016 Sep;48(9):995-1002. (PMID: 27479906)
      Cell. 2004 Apr 16;117(2):171-84. (PMID: 15084256)
      Annu Rev Genet. 2011;45:167-202. (PMID: 21854230)
      Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16161-6. (PMID: 22988065)
      Diabetes. 2003 Mar;52(3):717-25. (PMID: 12606513)
      J Immunol. 2000 Oct 1;165(7):3706-12. (PMID: 11034375)
      J Immunol Methods. 2013 Dec 31;400-401:13-22. (PMID: 24239865)
      Nat Rev Immunol. 2011 Apr;11(4):251-63. (PMID: 21394103)
      Mol Immunol. 2007 Mar;44(9):2378-87. (PMID: 17156844)
      J Immunol. 2009 Jul 1;183(1):59-65. (PMID: 19535636)
      Front Immunol. 2016 Sep 27;7:388. (PMID: 27729912)
      Science. 1995 May 26;268(5214):1185-8. (PMID: 7761837)
      Int Immunol. 1994 Nov;6(11):1681-6. (PMID: 7865461)
      Mol Aspects Med. 2015 Apr;42:42-60. (PMID: 25579746)
      Diabetes. 2002 May;51(5):1375-82. (PMID: 11978633)
      Front Immunol. 2013 Aug 07;4:232. (PMID: 23966994)
      Nat Rev Immunol. 2004 Feb;4(2):123-32. (PMID: 15040585)
      Int Immunol. 2004 Mar;16(3):423-31. (PMID: 14978016)
      Nat Med. 2005 Oct;11(10):1118-24. (PMID: 16186818)
      J Immunol Methods. 2012 Jan 31;375(1-2):14-9. (PMID: 21945395)
      J Immunol. 2008 Dec 1;181(11):7853-62. (PMID: 19017975)
      J Clin Invest. 2004 Feb;113(3):451-63. (PMID: 14755342)
      Science. 1993 Aug 27;261(5125):1175-8. (PMID: 8356452)
      Diabetes. 2011 Aug;60(8):2112-9. (PMID: 21659501)
      Diabetes. 2004 Aug;53(8):1987-94. (PMID: 15277377)
      Aging Dis. 2012 Jun;3(3):280-90. (PMID: 22724086)
      Mol Biotechnol. 2008 Sep;40(1):101-11. (PMID: 18463990)
      Nat Commun. 2013;4:2680. (PMID: 24157944)
      Nat Methods. 2009 Nov;6(11):786-7. (PMID: 19876014)
      Nat Commun. 2016 Apr 04;7:11153. (PMID: 27040081)
      Cell. 2015 Aug 13;162(4):751-65. (PMID: 26234156)
      Nature. 2007 Sep 27;449(7161):483-6. (PMID: 17898768)
      Diabetes. 2015 Jan;64(1):172-82. (PMID: 25157096)
      J Immunol. 2004 Sep 15;173(6):4009-19. (PMID: 15356150)
      Nat Rev Immunol. 2016 Apr;16(4):234-46. (PMID: 26996199)
      Nature. 2007 Dec 13;450(7172):1106-10. (PMID: 18033247)
      J Immunol. 2014 Mar 15;192(6):2689-98. (PMID: 24510963)
      Pediatrics. 2010 Nov;126(5):e1248-52. (PMID: 20956421)
      Diabetologia. 1981 Feb;20(2):87-93. (PMID: 7193616)
      Diabetes. 2006 Jan;55(1):50-60. (PMID: 16380476)
      Nat Immunol. 2016 Aug;17 (8):946-55. (PMID: 27348411)
      Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5980-5. (PMID: 24711416)
      Front Immunol. 2013 Dec 25;4:466. (PMID: 24400005)
      Lancet. 2016 Jun 4;387(10035):2331-2339. (PMID: 27302272)
      Lancet. 2016 Jun 4;387(10035):2340-2348. (PMID: 27302273)
      Mol Cell Biol. 2002 May;22(10):3460-73. (PMID: 11971977)
      J Immunol. 2015 Mar 15;194(6):2531-8. (PMID: 25681349)
      Diabetes. 2005 Dec;54 Suppl 2:S125-36. (PMID: 16306330)
      Blood. 2009 Nov 5;114(19):4099-107. (PMID: 19706884)
      Nat Protoc. 2006;1(1):1-6. (PMID: 17406204)
      Nat Genet. 1997 Mar;15(3):293-7. (PMID: 9054945)
      Science. 2002 Nov 15;298(5597):1395-401. (PMID: 12376594)
      Genes Immun. 2015 Sep;16(6):388-98. (PMID: 26043173)
      Diabetes. 2010 Jun;59(6):1451-60. (PMID: 20299476)
      Front Immunol. 2013 Dec 25;4:463. (PMID: 24400004)
      Nat Rev Immunol. 2008 Mar;8(3):231-8. (PMID: 18301425)
      Lancet. 2014 Jan 4;383(9911):69-82. (PMID: 23890997)
      Genome Med. 2013 Oct 30;5(10):98. (PMID: 24172704)
      Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9875-80. (PMID: 24941953)
      Eur J Immunol. 2013 Aug;43(8):2185-93. (PMID: 23670527)
      Nat Immunol. 2015 Jun;16(6):628-34. (PMID: 25939024)
      J Clin Invest. 2015 Nov 2;125(11):4135-48. (PMID: 26457731)
      J Immunol. 2013 Dec 1;191(11):5430-40. (PMID: 24163407)
      J Allergy Clin Immunol. 2014 Mar;133(3):880-2.e10. (PMID: 24472623)
      BMC Bioinformatics. 2015 May 28;16:175. (PMID: 26017500)
      Immunol Rev. 2004 Aug;200:44-56. (PMID: 15242395)
      Clin Exp Immunol. 2015 Mar;179(3):398-413. (PMID: 25302633)
    • Accession Number:
      0 (Autoantigens)
      0 (Complementarity Determining Regions)
      0 (Receptors, Antigen, T-Cell, alpha-beta)
    • Publication Date:
      Date Created: 20171128 Date Completed: 20180919 Latest Revision: 20181113
    • Publication Date:
      20221213
    • Accession Number:
      PMC5702608
    • Accession Number:
      10.1038/s41467-017-01925-2
    • Accession Number:
      29176645