title: Tracking phenotypically and functionally distinct T cell subsets via T cell repertoire diversity.
abstract: Antigen-specific T cell receptors (TCRs) recognise complexes of immunogenic peptides (p) and major histocompatibility complex (MHC) glycoproteins. Responding T cell populations show profiles of preferred usage (or bias) toward one or few TCRbeta chains. Such skewing is also observed, though less commonly, in TCRalpha chain usage. The extent and character of clonal diversity within individual, antigen-specific T cell sets can be established by sequence analysis of the TCRVbeta and/or TCRValpha CDR3 loops. The present review provides examples of such TCR repertoires in prominent responses to acute and persistent viruses. The determining role of structural constraints and antigen dose is discussed, as is the way that functionally and phenotypically distinct populations can be defined at the clonal level. In addition, clonal dissection of "high" versus "low" avidity, or "central" versus "effector" memory sets provides insights into how these antigen specific T cell responses are generated and maintained. As TCR diversity potentially influences both the protective capacity of CD8+ T cells and the subversion of immune control that leads to viral escape, analysing the spectrum of TCR selection and maintenance has implications for improving the functional efficacy of T cell responsiveness and effector function.
authors: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Melbourne, Australia.
authors: Katherine
authors: K
authors: Kedzierska
authors: Nicole L
authors: NL
authors: La Gruta
authors: John
authors: J
authors: Stambas
authors: Stephen J
authors: SJ
authors: Turner
authors: Peter C
authors: PC
authors: Doherty
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology; D014780:Viruses / Q000276:immunology*
chemical_list: D022801:Complementarity Determining Regions; D006649:Histocompatibility Antigens; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta
references: J Biol Chem. 2005 Jun 24;280(25):23900-9
references: 15849183
references: J Exp Med. 2005 Jul 4;202(1):123-33
references: 15983064
references: J Immunol. 2005 Jul 15;175(2):855-63
references: 16002683
references: Nat Immunol. 2005 Aug;6(8):793-9
references: 16025119
references: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11432-7
references: 16061802
references: J Immunol. 2005 Nov 1;175(9):6123-32
references: 16237109
references: Nat Immunol. 2005 Nov;6(11):1114-22
references: 16186824
references: J Exp Med. 2005 Nov 21;202(10):1349-61
references: 16287711
references: Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):994-9
references: 16418289
references: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9184-9
references: 16754852
references: Immunol Rev. 2006 Jun;211:133-45
references: 16824123
references: J Immunol. 2006 Nov 15;177(10):6705-12
references: 17082583
references: Eur J Immunol. 2006 Nov;36(11):2951-9
references: 17072910
references: Nat Rev Immunol. 2006 Dec;6(12):883-94
references: 17110956
references: Immunity. 2004 Dec;21(6):793-803
references: 15589168
references: Nature. 1999 Oct 14;401(6754):708-12
references: 10537110
references: Science. 1999 Oct 29;286(5441):958-61
references: 10542151
references: Immunity. 2003 Jan;18(1):53-64
references: 12530975
references: Immunity. 2003 Feb;18(2):193-204
references: 12594947
references: Nat Immunol. 2003 Mar;4(3):225-34
references: 12563257
references: Immunity. 2003 Apr;18(4):549-59
references: 12705857
references: Nat Immunol. 2003 Jul;4(7):657-63
references: 12796775
references: Immunity. 2004 Jan;20(1):5-16
references: 14738760
references: Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4942-7
references: 15037737
references: J Exp Med. 1987 Mar 1;165(3):591-600
references: 3493320
references: Nature. 1987 Apr 30-May 6;326(6116):881-2
references: 2437457
references: Cell. 1988 Jul 15;54(2):263-73
references: 2455603
references: Cell. 1988 Aug 12;54(4):577-92
references: 2456857
references: EMBO J. 1988 Dec 1;7(12):3745-55
references: 3208747
references: J Immunol. 1990 May 15;144(10):3980-6
references: 1692070
references: J Virol. 1990 Dec;64(12):5919-26
references: 1700830
references: Nature. 1991 May 23;351(6324):290-6
references: 1709722
references: Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8987-90
references: 1833769
references: Eur J Immunol. 1992 Apr;22(4):903-7
references: 1372560
references: Proc Natl Acad Sci U S A. 1993 May 1;90(9):4319-23
references: 8483950
references: J Immunol. 1993 Sep 1;151(5):2658-66
references: 7689611
references: Cell. 1994 Jan 14;76(1):39-50
references: 7506996
references: J Exp Med. 1994 Apr 1;179(4):1155-61
references: 7511682
references: Nature. 1994 Aug 11;370(6489):463-7
references: 8047166
references: J Exp Med. 2000 Jan 17;191(2):335-46
references: 10637277
references: J Virol. 2000 Apr;74(8):3486-93
references: 10729122
references: J Immunol. 2000 Jun 1;164(11):5782-7
references: 10820256
references: Annu Rev Immunol. 2000;18:561-92
references: 10837069
references: Immunity. 2000 May;12(5):547-56
references: 10843387
references: J Immunol. 2000 Sep 1;165(5):2404-9
references: 10946264
references: Science. 2000 Oct 6;290(5489):92-7
references: 11021806
references: J Immunol. 2000 Dec 1;165(11):6081-90
references: 11086040
references: Nature. 2001 Mar 1;410(6824):101-5
references: 11242050
references: Science. 1995 Apr 7;268(5207):106-11
references: 7535476
references: Immunol Today. 1995 Apr;16(4):176-81
references: 7734044
references: Cell Immunol. 1995 May;162(2):340
references: 7743562
references: J Virol. 1995 Sep;69(9):5849-52
references: 7543591
references: Ann N Y Acad Sci. 1995 Jul 7;756:1-11
references: 7645810
references: J Exp Med. 1995 Dec 1;182(6):1703-15
references: 7500015
references: Immunogenetics. 1995;42(6):501-30
references: 8550093
references: Immunity. 1996 Jan;4(1):47-55
references: 8574851
references: Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4102-7
references: 8633023
references: Nat Med. 1996 Aug;2(8):906-11
references: 8705861
references: Science. 1996 Oct 11;274(5285):209-19
references: 8824178
references: J Virol. 1996 Nov;70(11):7569-79
references: 8892876
references: Nature. 1996 Nov 14;384(6605):134-41
references: 8906788
references: Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9848-53
references: 9275214
references: J Exp Med. 1998 May 18;187(10):1647-57
references: 9584143
references: J Exp Med. 1998 Jul 6;188(1):61-70
references: 9653084
references: J Exp Med. 1998 Jul 6;188(1):71-82
references: 9653085
references: Immunity. 1998 Jun;8(6):675-82
references: 9655481
references: J Exp Med. 1998 Dec 7;188(11):1993-2005
references: 9841914
references: J Immunol. 1999 Jan 15;162(2):989-94
references: 9916724
references: J Immunol. 1999 Feb 15;162(4):2227-34
references: 9973498
references: J Exp Med. 1999 Feb 15;189(4):701-10
references: 9989985
references: Immunity. 1999 Jan;10(1):1-7
references: 10023765
references: J Exp Med. 1999 Jun 7;189(11):1823-38
references: 10359586
references: J Virol. 1999 Sep;73(9):7619-26
references: 10438852
references: Immunity. 2004 Nov;21(5):669-79
references: 15539153
references: J Mol Biol. 2005 Feb 4;345(5):1099-110
references: 15644207
references: J Exp Med. 2005 Feb 21;201(4):579-90
references: 15710650
references: J Exp Med. 2005 Feb 21;201(4):523-33
references: 15710651
references: Nat Immunol. 2005 Apr;6(4):382-9
references: 15735650
references: Science. 2001 Mar 23;291(5512):2413-7
references: 11264538
references: Nat Immunol. 2001 Aug;2(8):711-7
references: 11477407
references: J Immunol Methods. 2002 Mar 1;261(1-2):177-94
references: 11861076
references: J Immunol. 2002 Apr 15;168(8):4231-40
references: 11937585
references: Science. 2002 Nov 29;298(5599):1797-800
references: 12459592
references: Nat Rev Immunol. 2002 Dec;2(12):982-7
references: 12461571
references: J Immunol. 2004 May 1;172(9):5553-60
references: 15100298
references: Semin Immunol. 2004 Jun;16(3):179-84
references: 15130502
references: J Immunol. 2004 Jul 1;173(1):402-9
references: 15210799
references: Int Immunol. 2004 Nov;16(11):1549-59
references: 15351787
references: Nature. 1984 Jun 28-Jul 4;309(5971):757-62
references: 6330561
references: Cell. 1984 Jul;37(3):1101-10
references: 6611207
references: Nature. 1984 Aug 2-8;310(5976):387-91
references: 6336329
references: Cell. 1986 Mar 28;44(6):959-68
references: 2420472
references: J Exp Med. 1994 Dec 1;180(6):2335-40
references: 7964506
references: J Exp Med. 1995 Jan 1;181(1):79-91
references: 7807026