Models of Self-Peptide Sampling by Developing T Cells Identify Candidate Mechanisms of Thymic Selection

PLoS Computational Biology

Volumn 9, Issue 7, 2013, Pages

  Bains, Iren ^a,b   van Santen, Hisse M ^c   Seddon, Benedict ^a   Yates, Andrew J ^b  

^a NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^c UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGENS; CYTOLOGY; LIGANDS; STOCHASTIC MODELS; STOCHASTIC SYSTEMS; T-CELLS; THYMUS;

CANDIDATE MECHANISMS; CELL-BE; CELL/B.E; CELL/BE; EXPOSED TO; FOREIGN ANTIGENS; KEY ELEMENTS; PROBABILISTIC PROCESS; SPECTRA'S; THYMIC SELECTION;

PEPTIDES;

CD4 ANTIGEN; MAJOR HISTOCOMPATIBILITY ANTIGEN; T LYMPHOCYTE RECEPTOR;

ARTICLE; CD4+ T LYMPHOCYTE; CELL FATE; CELL GROWTH; CELL LINEAGE; CELL SELECTION; DEVELOPMENTAL STAGE; MATHEMATICAL ANALYSIS; PEPTIDE ANALYSIS; QUANTITATIVE ANALYSIS; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; STOCHASTIC MODEL; T LYMPHOCYTE; THYMOCYTE; THYMUS;

EID: 84880835331     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1003102     Document Type: Article

References (77)

1. Wing K, Sakaguchi S, (2010) Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 11: 7-13.
2. Williams CB, Engle DL, Kersh GJ, Michael White J, Allen PM, (1999) A kinetic threshold between negative and positive selection based on the longevity of the T cell receptor-ligand complex. J Exp Med 189: 1531-44.
3. Daniels MA, Teixeiro E, Gill J, Hausmann B, Roubaty D, et al. (2006) Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling. Nature 444: 724-9.
4. Maloy KJ, Powrie F, (2001) Regulatory T cells in the control of immune pathology. Nat Immunol 2: 816-22.
5. Hsieh CS, Liang Y, Tyznik AJ, Self SG, Liggitt D, et al. (2004) Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity 21: 267-77.
6. Bettini ML, Vignali DAA, (2010) Development of thymically derived natural regulatory T cells. Ann N Y Acad Sci 1183: 1-12.
7. Romagnoli P, van Meerwijk JPM, (2010) Thymic selection and lineage commitment of CD4(+)Foxp3(+) regulatory T lymphocytes. Prog Mol Biol Transl Sci 92: 251-77.
8. Wong J, Obst R, Correia-Neves M, Losyev G, Mathis D, et al. (2007) Adaptation of TCR repertoires to self-peptides in regulatory and nonregulatory CD4+ T cells. J Immunol 178: 7032-41.
9. Jordan MS, Boesteanu A, Reed AJ, Petrone AL, Holenbeck AE, et al. (2001) Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2: 301-6.
10. Apostolou I, Sarukhan A, Klein L, von Boehmer H, (2002) Origin of regulatory T cells with known specificity for antigen. Nat Immunol 3: 756-63.
11. Kawahata K, Misaki Y, Yamauchi M, Tsunekawa S, Setoguchi K, et al. (2002) Generation of CD4(+)CD25(+) regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonautoreactive T cells by endogenous TCR expression. J Immunol 168: 4399-405.
12. Aschenbrenner K, D'Cruz LM, Vollmann EH, Hinterberger M, Emmerich J, et al. (2007) Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat Immunol 8: 351-8.
13. Larkin J 3rd, Rankin AL, Picca CC, Riley MP, Jenks SA, et al. (2008) CD4+CD25+ regulatory T cell repertoire formation shaped by differential presentation of peptides from a self-antigen. J Immunol 180: 2149-57.
14. Lee HM, Bautista JL, Scott-Browne J, Mohan JF, Hsieh CS, (2012) A broad range of self-reactivity drives thymic regulatory T cell selection to limit responses to self. Immunity 37: 475-86.
15. Cozzo Picca C, Simons DM, Oh S, Aitken M, Perng OA, et al. (2011) CD4+CD25+Foxp3+ regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion. Proc Natl Acad Sci U S A 108: 14890-5.
16. van Santen HM, Benoist C, Mathis D, (2004) Number of T reg cells that differentiate does not increase upon encounter of agonist ligand on thymic epithelial cells. J Exp Med 200: 1221-30.
17. Cozzo Picca C, Oh S, Panarey L, Aitken M, Basehoar A, et al. (2009) Thymocyte deletion can bias Treg formation toward low-abundance self-peptide. Eur J Immunol 39: 3301-6.
18. Atibalentja DF, Byersdorfer CA, Unanue ER, (2009) Thymus-blood protein interactions are highly effective in negative selection and regulatory T cell induction. J Immunol 183: 7909-18.
19. Sebzda E, Wallace VA, Mayer J, Yeung RS, Mak TW, et al. (1994) Positive and negative thymocyte selection induced by different concentrations of a single peptide. Science 263: 1615-8.
20. Lerman MA, Larkin J 3rd, Cozzo C, Jordan MS, Caton AJ, (2004) CD4+ CD25+ regulatory T cell repertoire formation in response to varying expression of a neo-self-antigen. J Immunol 173: 236-44.
21. Feuerer M, Jiang W, Holler PD, Satpathy A, Campbell C, et al. (2007) Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetes. Proc Natl Acad Sci U S A 104: 18181-6.
22. Bautista JL, Lio CWJ, Lathrop SK, Forbush K, Liang Y, et al. (2009) Intraclonal competition limits the fate determination of regulatory T cells in the thymus. Nat Immunol 10: 610-7.
23. Leung MWL, Shen S, Lafaille JJ, (2009) TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes. J Exp Med 206: 2121-30.
24. Moran AE, Holzapfel KL, Xing Y, Cunningham NR, Maltzman JS, et al. (2011) T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J Exp Med 208: 1279-89.
25. Eck SC, Zhu P, Pepper M, Bensinger SJ, Freedman BD, et al. (2006) Developmental alterations in thymocyte sensitivity are actively regulated by MHC class II expression in the thymic medulla. J Immunol 176: 2229-37.
26. Stephen TL, Tikhonova A, Riberdy JM, Laufer TM, (2009) The activation threshold of CD4+ T cells is defined by TCR/peptide-MHC class II interactions in the thymic medulla. J Immunol 183: 5554-62.
27. Azzam HS, DeJarnette JB, Huang K, Emmons R, Park CS, et al. (2001) Fine tuning of TCR signaling by CD5. J Immunol 166: 5464-72.
28. Saini M, Sinclair C, Marshall D, Tolaini M, Sakaguchi S, et al. (2010) Regulation of Zap70 expressionduring thymocyte development enables temporal separation of CD4 and CD8 repertoire selection at different signaling thresholds. Sci Signal 3: ra23.
29. Neilson JR, Zheng GXY, Burge CB, Sharp PA, (2007) Dynamic regulation of miRNA expression in ordered stages of cellular development. Genes Dev 21: 578-89.
30. Li QJ, Chau J, Ebert PJR, Sylvester G, Min H, et al. (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129: 147-61.
31. Davey GM, Schober SL, Endrizzi BT, Dutcher AK, Jameson SC, et al. (1998) Preselection thymocytes are more sensitive to T cell receptor stimulation than mature T cells. J Exp Med 188: 1867-74.
32. Chao DL, Davenport MP, Forrest S, Perelson AS, (2005) The effects of thymic selection on the range of T cell cross-reactivity. Eur J Immunol 35: 3452-9.
33. Kosmrlj A, Jha AK, Huseby ES, Kardar M, Chakraborty AK, (2008) How the thymus designs antigen-specific and self-tolerant T cell receptor sequences. Proc Natl Acad Sci U S A 105: 16671-6.
34. Detours V, Perelson AS, (1999) Explaining high alloreactivity as a quantitative consequence of affinity-driven thymocyte selection. Proc Natl Acad Sci U S A 96: 5153-8.
35. Detours V, Mehr R, Perelson AS, (2000) Deriving quantitative constraints on T cell selection from data on the mature T cell repertoire. J Immunol 164: 121-8.
36. Faro J, Velasco S, González-Fernández A, Bandeira A, (2004) The impact of thymic antigen diversity on the size of the selected T cell repertoire. J Immunol 172: 2247-55.
37. Souza-e Silva H, Savino W, Feijóo RA, Vasconcelos ATR, (2009) A cellular automata-based mathematical model for thymocyte development. PLoS One 4: e8233.
38. Kosmrlj A, Read EL, Qi Y, Allen TM, Altfeld M, et al. (2010) Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection. Nature 465: 350-4.
39. Borghans JAM, Noest AJ, De Boer RJ, (2003) Thymic selection does not limit the individual MHC diversity. Eur J Immunol 33: 3353-8.
40. McKeithan TW, (1995) Kinetic proofreading in T-cell receptor signal transduction. Proc Natl Acad Sci U S A 92: 5042-6.
41. Germain RN, Stefanová I, (1999) The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation. Annu Rev Immunol 17: 467-522.
42. Valitutti S, Müller S, Dessing M, Lanzavecchia A, (1996) Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J Exp Med 183: 1917-21.
43. Rosette C, Werlen G, Daniels MA, Holman PO, Alam SM, et al. (2001) The impact of duration versus extent of TCR occupancy on T cell activation: a revision of the kinetic proofreading model. Immunity 15: 59-70.
44. Labrecque N, Whitfield LS, Obst R, Waltzinger C, Benoist C, et al. (2001) How much TCR does a T cell need? Immunity 15: 71-82.
45. Stone JD, Chervin AS, Kranz DM, (2009) T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity. Immunology 126: 165-76.
46. Prasad A, Zikherman J, Das J, Roose JP, Weiss A, et al. (2009) Origin of the sharp boundary that discriminates positive and negative selection of thymocytes. Proc Natl Acad Sci U S A 106: 528-33.
47. Altan-Bonnet G, Germain RN, (2005) Modeling T cell antigen discrimination based on feedback control of digital ERK responses. PLoS Biol 3: e356.
48. Currie J, Castro M, Lythe G, Palmer E, Molina-París C, (2012) A stochastic T cell response criterion. J R Soc Interface 9: 2856-70.
49. Govern CC, Paczosa MK, Chakraborty AK, Huseby ES, (2010) Fast on-rates allow short dwell time ligands to activate T cells. Proc Natl Acad Sci U S A 107: 8724-9.
50. Underhill DM, Bassetti M, Rudensky A, Aderem A, (1999) Dynamic interactions of macrophages with T cells during antigen presentation. J Exp Med 190: 1909-14.
51. Friedl P, Gunzer M, (2001) Interaction of T cells with APCs: the serial encounter model. Trends Immunol 22: 187-91.
52. Gunzer M, Schäfer A, Borgmann S, Grabbe S, Zänker KS, et al. (2000) Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity 13: 323-32.
53. Mempel TR, Henrickson SE, Von Andrian UH, (2004) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427: 154-9.
54. Kawahata K, Misaki Y, Yamauchi M, Tsunekawa S, Setoguchi K, et al. (2002) Generation of CD4(+)CD25(+) regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonautoreactive T cells by endogenous TCR expression. J Immunol 168: 4399-405.
55. Nadarajah S, (2008) A review of results on sums of random variables. Acta Appl Math 103: 131-140.
56. Fisher RA, Tippet LHC, (1928) Limiting forms of the frequency distribution of the largest or smallest member of a sample. Proc Cambridge Phil Soc 24: 180-190.
57. Gnedenko PB, (1943) Sur la distribution limite du terme maximum d'une serie aleatoire. Annals of Mathematics 44: 423-453.
58. Obst R, van Santen HM, Mathis D, Benoist C, (2005) Antigen persistence is required throughout the expansion phase of a CD4(+) T cell response. J Exp Med 201: 1555-65.
59. Le Borgne M, Ladi E, Dzhagalov I, Herzmark P, Liao YF, et al. (2009) The impact of negative selection on thymocyte migration in the medulla. Nat Immunol 10: 823-30.
60. Irvine DJ, Purbhoo MA, Krogsgaard M, Davis MM, (2002) Direct observation of ligand recognition by T cells. Nature 419: 845-9.
61. Brower RC, England R, Takeshita T, Kozlowski S, Margulies DH, et al. (1994) Minimal requirements for peptide mediated activation of CD8+ CTL. Mol Immunol 31: 1285-93.
62. Naeher D, Daniels MA, Hausmann B, Guillaume P, Luescher I, et al. (2007) A constant affinity threshold for T cell tolerance. J Exp Med 204: 2553-9.
63. Hogquist KA, Jameson SC, Heath WR, Howard JL, Bevan MJ, et al. (1994) T cell receptor antagonist peptides induce positive selection. Cell 76: 17-27.
64. Liu CP, Crawford F, Marrack P, Kappler J, (1998) T cell positive selection by a high density, low affinity ligand. Proc Natl Acad Sci U S A 95: 4522-6.
65. Nikolić-Zugić J, Bevan MJ, (1990) Role of self-peptides in positively selecting the T-cell repertoire. Nature 344: 65-7.
66. Lio CWJ, Hsieh CS, (2008) A two-step process for thymic regulatory T cell development. Immunity 28: 100-11.
67. Burchill MA, Yang J, Vang KB, Moon JJ, Chu HH, et al. (2008) Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity 28: 112-21.
68. Cheng G, Yu A, Dee MJ, Malek TR, (2013) IL-2R signaling is essential for functional maturation of regulatory T cells during thymic development. J Immunol 190: 1567-75.
69. Nishizuka Y, Sakakura T, (1969) Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166: 753-5.
70. Asano M, Toda M, Sakaguchi N, Sakaguchi S, (1996) Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med 184: 387-96.
71. Fontenot JD, Dooley JL, Farr AG, Rudensky AY, (2005) Developmental regulation of Foxp3 expression during ontogeny. J Exp Med 202: 901-6.
72. Lee HM, Hsieh CS, (2009) Rare development of Foxp3+ thymocytes in the CD4+CD8+ subset. J Immunol 183: 2261-6.
73. Cowan JE, Parnell SM, Nakamura K, Caamano JH, Lane PJL, et al. (2013) The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development. J Exp Med 210: 675-81.
74. Nakayama T, June CH, Munitz TI, Sheard M, McCarthy SA, et al. (1990) Inhibition of T cell receptor expression and function in immature CD4+CD8+ cells by CD4. Science 249: 1558-61.
75. Lorenz RG, Allen PM, (1989) Thymic cortical epithelial cells lack full capacity for antigen presentation. Nature 340: 557-9.
76. Mizuochi T, Kasai M, Kokuho T, Kakiuchi T, Hirokawa K, (1992) Medullary but not cortical thymic epithelial cells present soluble antigens to helper T cells. J Exp Med 175: 1601-5.
77. Gray DHD, Seach N, Ueno T, Milton MK, Liston A, et al. (2006) Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108: 3777-85.