title: gammadeltaTCR ligands and lineage commitment.
abstract: Two major T lymphocyte lineages--alphabeta and gammadelta T cells--develop in the thymus from common precursors. Differentiation of both lineages requires signals coming from TCRs. Development of alphabeta T cells is driven at early stages by signaling from the pre-TCR, most likely in a ligand-independent fashion, and later--by signals delivered by alphabetaTCRs binding to their ligands--classical or non-classical MHC molecules. gammadelta lineage cells likewise require TCR signaling for their differentiation. Recent work from several groups suggests that TCR signaling not only ensures the developmental progression towards alphabeta and gammadelta lineages but that signal strength instructs lineage fate: weaker TCR signal results in alphabeta and stronger--in gammadelta lineage commitment. However, as most gammadeltaTCRs remain orphan receptors, it is still debated whether strong signals from gammadeltaTCRs in development are generated in a ligand-dependent manner (as in the case of alphabetaTCRs), ligand-independent manner (as for pre-TCR) or both. Here we summarize evidence supporting a possible role for ligands in gammadelta T cell lineage commitment and the generation of gammadelta sublineages.
authors.affiliation: Laboratory of Lymphocyte Biology, Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Smith 736, Boston, MA 02115, USA.
authors.forename: Taras
authors.initials: T
authors.lastname: Kreslavsky
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
mesh_terms: D000818:Animals; D019070:Cell Lineage; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D006649:Histocompatibility Antigens; D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta
references.citation: Curr Opin Immunol. 2006 Oct;18(5):539-46
references.pmid: 16870417
references.citation: J Immunol. 2003 Sep 1;171(5):2413-20
references.pmid: 12928388
references.citation: Immunity. 2004 Jul;21(1):121-31
references.pmid: 15345225
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14741-6
references.pmid: 16203967
references.citation: Cell. 1989 May 19;57(4):667-74
references.pmid: 2524273
references.citation: Immunity. 2002 May;16(5):707-18
references.pmid: 12049722
references.citation: Scand J Immunol. 2003 Sep;58(3):374-81
references.pmid: 12950685
references.citation: Immunity. 2009 Oct 16;31(4):565-75
references.pmid: 19833086
references.citation: Nature. 1989 Aug 24;340(6235):646-50
references.pmid: 2528072
references.citation: J Exp Med. 2006 Jun 12;203(6):1543-50
references.pmid: 16754716
references.citation: Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):653-7
references.pmid: 1346234
references.citation: Adv Immunol. 2004;84:201-38
references.pmid: 15246254
references.citation: Nature. 1988 Aug 4;334(6181):395-402
references.pmid: 3043226
references.citation: Science. 2004 Oct 8;306(5694):269-71
references.pmid: 15472075
references.citation: Semin Immunol. 2010 Aug;22(4):207-13
references.pmid: 20430644
references.citation: Nat Immunol. 2008 Jul;9(7):777-84
references.pmid: 18516039
references.citation: Nature. 1986 Aug 28-Sep 3;322(6082):836-40
references.pmid: 2943999
references.citation: Nature. 1989 May 18;339(6221):230-1
references.pmid: 2654648
references.citation: J Exp Med. 1991 Jan 1;173(1):231-40
references.pmid: 1702138
references.citation: Immunity. 2005 Jan;22(1):71-80
references.pmid: 15664160
references.citation: Immunity. 2008 Mar;28(3):346-58
references.pmid: 18342007
references.citation: Nature. 1992 Nov 19;360(6401):225-31
references.pmid: 1359428
references.citation: Science. 2005 Apr 8;308(5719):227-31
references.pmid: 15821084
references.citation: Science. 2005 Apr 8;308(5719):252-5
references.pmid: 15821090
references.citation: Science. 1998 Mar 13;279(5357):1737-40
references.pmid: 9497295
references.citation: Nature. 2000 Aug 3;406(6795):524-7
references.pmid: 10952314
references.citation: Eur J Immunol. 1992 Feb;22(2):491-8
references.pmid: 1311262
references.citation: Immunity. 2006 Jul;25(1):105-16
references.pmid: 16814577
references.citation: J Immunol. 2009 Feb 15;182(4):1892-900
references.pmid: 19201842
references.citation: J Immunol. 2010 Feb 1;184(3):1268-79
references.pmid: 20038637
references.citation: Immunity. 2008 Sep 19;29(3):391-403
references.pmid: 18703361
references.citation: Science. 2004 Jul 9;305(5681):248-51
references.pmid: 15247480
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Mar 25;786(1-2):297-304
references.pmid: 12651026
references.citation: Nat Immunol. 2008 Sep;9(9):1055-64
references.pmid: 18660811
references.citation: Immunity. 1996 Oct;5(4):343-52
references.pmid: 8885867
references.citation: J Immunol. 2009 May 1;182(9):5306-16
references.pmid: 19380777
references.citation: Eur J Immunol. 1997 Feb;27(2):544-53
references.pmid: 9045929
references.citation: Cell. 1990 Aug 10;62(3):549-61
references.pmid: 2379238
references.citation: Cell. 1990 Oct 19;63(2):333-40
references.pmid: 2208290
references.citation: Proc Natl Acad Sci U S A. 1989 Aug;86(15):5928-32
references.pmid: 2788280
references.citation: J Exp Med. 1997 Oct 20;186(8):1269-75
references.pmid: 9334366
references.citation: J Immunol. 1994 Feb 15;152(4):1578-88
references.pmid: 8120371
references.citation: Teratology. 1999 Oct;60(4):226-39
references.pmid: 10508976
references.citation: Mol Cell Biol. 2006 Jun;26(12):4642-51
references.pmid: 16738328
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12453-8
references.pmid: 19617548
references.citation: PLoS One. 2010 Feb 19;5(2):e9303
references.pmid: 20174563
references.citation: PLoS One. 2008 Jan 30;3(1):e1512
references.pmid: 18231598
references.citation: J Immunol. 2004 Dec 1;173(11):6515-20
references.pmid: 15557139
references.citation: Nat Immunol. 2006 Sep;7(9):995-1003
references.pmid: 16878135
references.citation: J Autoimmun. 2010 Jun;34(4):478-84
references.pmid: 20080388
references.citation: J Immunol. 2009 May 1;182(9):5165-9
references.pmid: 19380758
references.citation: Eur J Immunol. 1993 Jul;23(7):1615-22
references.pmid: 8391987
references.citation: Science. 1999 Jul 30;285(5428):727-9
references.pmid: 10426993
references.citation: J Exp Med. 1999 Dec 20;190(12):1801-12
references.pmid: 10601355
references.citation: Curr Opin Immunol. 2010 Apr;22(2):185-92
references.pmid: 20074925
references.citation: Eur J Immunol. 1992 Feb;22(2):483-9
references.pmid: 1371469
references.citation: J Exp Med. 2001 Mar 19;193(6):689-98
references.pmid: 11257136
references.citation: Nat Immunol. 2006 Aug;7(8):843-50
references.pmid: 16829962
references.citation: Immunity. 1998 Apr;8(4):427-38
references.pmid: 9586633
references.citation: J Immunol. 1992 Mar 1;148(5):1302-7
references.pmid: 1371523
references.citation: J Exp Med. 2000 Aug 21;192(4):537-48
references.pmid: 10952723
references.citation: Curr Opin Immunol. 2006 Oct;18(5):527-33
references.pmid: 16879956
references.citation: Science. 1997 Jun 27;276(5321):2057-62
references.pmid: 9197272
references.citation: J Immunol. 2004 Sep 1;173(5):3261-70
references.pmid: 15322188
references.citation: Nature. 2000 Mar 30;404(6777):506-10
references.pmid: 10761920
references.citation: J Exp Med. 1994 Jan 1;179(1):323-8
references.pmid: 8270877
references.citation: Immunity. 2005 May;22(5):595-606
references.pmid: 15894277
references.citation: Immunity. 2005 May;22(5):583-93
references.pmid: 15894276
references.citation: J Immunol. 2000 Aug 15;165(4):1790-8
references.pmid: 10925256
references.citation: Cell. 1992 May 1;69(3):529-37
references.pmid: 1316241
references.citation: Immunity. 1997 Jul;7(1):123-34
references.pmid: 9252125
references.citation: Eur J Immunol. 2009 Jul;39(7):1937-46
references.pmid: 19585514
references.citation: Science. 2007 Jan 12;315(5809):230-3
references.pmid: 17218525
references.citation: Immunity. 1996 Sep;5(3):217-28
references.pmid: 8808677
references.citation: J Immunol. 2002 Aug 1;169(3):1236-40
references.pmid: 12133944
references.citation: J Exp Med. 2002 Apr 1;195(7):855-67
references.pmid: 11927630
references.citation: Nature. 1989 Dec 7;342(6250):696-8
references.pmid: 2594068
references.citation: J Immunol. 2004 Apr 1;172(7):4167-75
references.pmid: 15034029
references.citation: J Exp Med. 1997 May 5;185(9):1541-7
references.pmid: 9151891
references.citation: Science. 1989 Aug 18;245(4919):746-9
references.pmid: 2528206
references.citation: Cancer Invest. 2004;22(1):106-16
references.pmid: 15069768
references.citation: J Immunol. 2004 Mar 15;172(6):3573-9
references.pmid: 15004158
references.citation: Immunol Rev. 2007 Feb;215:77-88
references.pmid: 17291280
references.citation: Nature. 1995 May 11;375(6527):155-8
references.pmid: 7753173
references.citation: Nat Immunol. 2005 Nov;6(11):1079-86
references.pmid: 16239924
references.citation: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4348-52
references.pmid: 1584768
references.citation: Immunity. 2008 Jul 18;29(1):90-100
references.pmid: 18585064
references.citation: Nat Immunol. 2006 Jan;7(1):67-75
references.pmid: 16327787
references.citation: Nat Genet. 2008 May;40(5):656-62
references.pmid: 18408721
references.citation: Mol Immunol. 2008 Jun;45(11):3253-63
references.pmid: 18455236
references.citation: Science. 1991 Jun 7;252(5011):1430-2
references.pmid: 1828619
references.citation: J Exp Med. 2008 May 12;205(5):1173-86
references.pmid: 18443226
references.citation: J Exp Med. 2000 Mar 20;191(6):937-48
references.pmid: 10727456