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Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes

Nature Immunology volume 8, pages 835–844 (2007)Cite this article

A Corrigendum to this article was published on 01 November 2007

This article has been updated

Abstract

T cells survey antigen-presenting dendritic cells (DCs) by migrating through DC networks, arresting and maintaining contact with DCs for several hours after encountering high-potency complexes of peptide and major histocompatibility complex (pMHC), leading to T cell activation. The effects of low-potency pMHC complexes on T cells in vivo, however, are unknown, as is the mechanism controlling T cell arrest. Here we evaluated T cell responses in vivo to high-, medium- and low-potency pMHC complexes and found that regardless of potency, pMHC complexes induced upregulation of CD69, anergy and retention of T cells in lymph nodes. However, only high-potency pMHC complexes expressed by DCs induced calcium-dependent T cell deceleration and calcineurin-dependent anergy. The pMHC complexes of lower potency instead induced T cell anergy by a biochemically distinct process that did not affect T cell dynamics.

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Figure 1: Activation of AND T cells in vivo by α-DEC-MCC and α-DEC-APL constructs.
Figure 2: Proliferation is not required for the induction of T cell anergy in vivo.
Figure 3: Potency of the pMHC complex drives early T cell deceleration.
Figure 4: T cell deceleration dependent on pMHC potency also depends on cytosolic Ca2+ flux.
Figure 5: Increased intracellular Ca2+ in AND T cells in the lymph nodes of mice treated with high-potency APL in vivo.
Figure 6: Effect of CsA and L-744832 on T cell anergy induced by pMHC complexes with various potencies.

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  • 19 October 2007

    In the version of this article initially published, the legends for Figures 1 and 5 are incorrect. The correct phrasing should be, for Figure 1a, “…injection of α-DEC-MCC, α-DEC-APL constructs, α-DEC-ovalbumin (α-DEC-OVA), α-DEC-205 plus isotype-MCC (α-DEC + iso-MCC) or PBS; for Figure 1b,c, “…injection of α-DEC-MCC, α-DEC-APL constructs, α-DEC-ovalbumin, α-DEC-205 plus isotype-MCC or PBS…”; and for Figure 5, “…mice were injected with α-DEC-APL constructs and then, 5 h later, with Fluo-4 AM– and CMRA-colabeled AND T cells” on line 2, and “Frequency of AND T cells with 'sustained' Ca2+ increase in mice treated…” on line 3. The errors have been corrected in the HTML and PDF versions of the article.

References

  1. Sloan-Lancaster, J. & Allen, P.M. Significance of T-cell stimulation by altered peptide ligands in T cell biology. Curr. Opin. Immunol. 7, 103–109 (1995).

    Article  CAS  Google Scholar 

  2. Madrenas, J. & Germain, R.N. Variant TCR ligands: new insights into the molecular basis of antigen-dependent signal transduction and T-cell activation. Semin. Immunol. 8, 83–101 (1996).

    Article  CAS  Google Scholar 

  3. Alam, S.M. et al. T-cell-receptor affinity and thymocyte positive selection. Nature 381, 616–620 (1996).

    Article  CAS  Google Scholar 

  4. Krogsgaard, M. et al. Evidence that structural rearrangements and/or flexibility during TCR binding can contribute to T cell activation. Mol. Cell 12, 1367–1378 (2003).

    Article  CAS  Google Scholar 

  5. Qi, S., Krogsgaard, M., Davis, M.M. & Chakraborty, A.K. Molecular flexibility can influence the stimulatory ability of receptor-ligand interactions at cell-cell junctions. Proc. Natl. Acad. Sci. USA 103, 4416–4421 (2006).

    Article  CAS  Google Scholar 

  6. Evavold, B.D. & Allen, P.M. Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science 252, 1308–1310 (1991).

    Article  CAS  Google Scholar 

  7. Sloan-Lancaster, J., Evavold, B.D. & Allen, P.M. Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells. Nature 363, 156–159 (1993).

    Article  CAS  Google Scholar 

  8. Daniels, M.A. et al. Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling. Nature 444, 724–729 (2006).

    Article  CAS  Google Scholar 

  9. Lyman, M.A. et al. The fate of low affinity tumor-specific CD8+ T cells in tumor-bearing mice. J. Immunol. 174, 2563–2572 (2005).

    Article  CAS  Google Scholar 

  10. Zehn, D. & Bevan, M.J. T cells with low avidity for a tissue-restricted antigen routinely evade central and peripheral tolerance and cause autoimmunity. Immunity 25, 261–270 (2006).

    Article  CAS  Google Scholar 

  11. Salazar-Gonzalez, R.M. et al. CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. Immunity 24, 623–632 (2006).

    Article  CAS  Google Scholar 

  12. Wei, S.H., Parker, I., Miller, M.J. & Cahalan, M.D. A stochastic view of lymphocyte motility and trafficking within the lymph node. Immunol. Rev. 195, 136–159 (2003).

    Article  CAS  Google Scholar 

  13. Sumen, C., Mempel, T.R., Mazo, I.B. & von Andrian, U.H. Intravital microscopy: visualizing immunity in context. Immunity 21, 315–329 (2004).

    CAS  PubMed  Google Scholar 

  14. Germain, R.N., Miller, M.J., Dustin, M.L. & Nussenzweig, M.C. Dynamic imaging of the immune system: progress, pitfalls and promise. Nat. Rev. Immunol. 6, 497–507 (2006).

    Article  CAS  Google Scholar 

  15. Miller, M.J., Wei, S.H., Cahalan, M.D. & Parker, I. Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc. Natl. Acad. Sci. USA 100, 2604–2609 (2003).

    Article  CAS  Google Scholar 

  16. Miller, M.J., Wei, S.H., Parker, I. & Cahalan, M.D. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296, 1869–1873 (2002).

    Article  CAS  Google Scholar 

  17. Miller, M.J., Hejazi, A.S., Wei, S.H., Cahalan, M.D. & Parker, I. T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node. Proc. Natl. Acad. Sci. USA 101, 998–1003 (2004).

    Article  CAS  Google Scholar 

  18. Lindquist, R.L. et al. Visualizing dendritic cell networks in vivo. Nat. Immunol. 5, 1243–1250 (2004).

    Article  CAS  Google Scholar 

  19. Bousso, P. & Robey, E. Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nat. Immunol. 4, 579–585 (2003).

    Article  CAS  Google Scholar 

  20. Bajenoff, M. et al. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25, 989–1001 (2006).

    Article  CAS  Google Scholar 

  21. Stoll, S., Delon, J., Brotz, T.M. & Germain, R.N. Dynamic imaging of T cell-dendritic cell interactions in lymph nodes. Science 296, 1873–1876 (2002).

    Article  Google Scholar 

  22. Mempel, T.R., Henrickson, S.E. & Von Andrian, U.H. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427, 154–159 (2004).

    Article  CAS  Google Scholar 

  23. Miller, M.J., Safrina, O., Parker, I. & Cahalan, M.D. Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J. Exp. Med. 200, 847–856 (2004).

    Article  CAS  Google Scholar 

  24. Hugues, S. et al. Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity. Nat. Immunol. 5, 1235–1242 (2004).

    Article  CAS  Google Scholar 

  25. Shakhar, G. et al. Stable T cell–dendritic cell interactions precede the development of both tolerance and immunity in vivo. Nat. Immunol. 6, 707–714 (2005).

    Article  CAS  Google Scholar 

  26. Castellino, F. et al. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell–dendritic cell interaction. Nature 440, 890–895 (2006).

    Article  CAS  Google Scholar 

  27. Grakoui, A. et al. The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221–227 (1999).

    Article  CAS  Google Scholar 

  28. Varma, R., Campi, G., Yokosuka, T., Saito, T. & Dustin, M.L. T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity 25, 117–127 (2006).

    Article  CAS  Google Scholar 

  29. Dustin, M.L. & Chan, A.C. Signaling takes shape in the immune system. Cell 103, 283–294 (2000).

    Article  CAS  Google Scholar 

  30. Iezzi, G., Karjalainen, K. & Lanzavecchia, A. The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8, 89–95 (1998).

    Article  CAS  Google Scholar 

  31. Obst, R., van Santen, H.M., Mathis, D. & Benoist, C. Antigen persistence is required throughout the expansion phase of a CD4+ T cell response. J. Exp. Med. 201, 1555–1565 (2005).

    Article  CAS  Google Scholar 

  32. Bhakta, N.R., Oh, D.Y. & Lewis, R.S. Calcium oscillations regulate thymocyte motility during positive selection in the three-dimensional thymic environment. Nat. Immunol. 6, 143–151 (2005).

    Article  CAS  Google Scholar 

  33. Negulescu, P.A., Krasieva, T.B., Khan, A., Kerschbaum, H.H. & Cahalan, M.D. Polarity of T cell shape, motility, and sensitivity to antigen. Immunity 4, 421–430 (1996).

    Article  CAS  Google Scholar 

  34. Matloubian, M. et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427, 355–360 (2004).

    Article  CAS  Google Scholar 

  35. Shiow, L.R. et al. CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 440, 540–544 (2006).

    Article  CAS  Google Scholar 

  36. Kaye, J. et al. Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor. Nature 341, 746–749 (1989).

    Article  CAS  Google Scholar 

  37. Rogers, P.R., Grey, H.M. & Croft, M. Modulation of naive CD4 T cell activation with altered peptide ligands: the nature of the peptide and presentation in the context of costimulation are critical for a sustained response. J. Immunol. 160, 3698–3704 (1998).

    CAS  PubMed  Google Scholar 

  38. Madrenas, J. et al. Zeta phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists. Science 267, 515–518 (1995).

    Article  CAS  Google Scholar 

  39. Hawiger, D. et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194, 769–779 (2001).

    Article  CAS  Google Scholar 

  40. Hawiger, D., Masilamani, R.F., Bettelli, E., Kuchroo, V.K. & Nussenzweig, M.C. Immunological unresponsiveness characterized by increased expression of CD5 on peripheral T cells induced by dendritic cells in vivo. Immunity 20, 695–705 (2004).

    Article  CAS  Google Scholar 

  41. Dustin, M.L., Bromley, S.K., Kan, Z., Peterson, D.A. & Unanue, E.R. Antigen receptor engagement delivers a stop signal to migrating T lymphocytes. Proc. Natl. Acad. Sci. USA 94, 3909–3913 (1997).

    Article  CAS  Google Scholar 

  42. Bromley, S.K., Peterson, D.A., Gunn, M.D. & Dustin, M.L. Cutting edge: hierarchy of chemokine receptor and TCR signals regulating T cell migration and proliferation. J. Immunol. 165, 15–19 (2000).

    Article  CAS  Google Scholar 

  43. Qi, H., Egen, J.G., Huang, A.Y. & Germain, R.N. Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science 312, 1672–1676 (2006).

    Article  CAS  Google Scholar 

  44. Dudziak, D. et al. Differential antigen processing by dendritic cell subsets in vivo. Science 315, 107–111 (2007).

    Article  CAS  Google Scholar 

  45. Heissmeyer, V. et al. Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat. Immunol. 5, 255–265 (2004).

    Article  CAS  Google Scholar 

  46. Zha, Y. et al. T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-α. Nat. Immunol. 7, 1166–1173 (2006).

    Article  CAS  Google Scholar 

  47. Chiodetti, L., Choi, S., Barber, D.L. & Schwartz, R.H. Adaptive tolerance and clonal anergy are distinct biochemical states. J. Immunol. 176, 2279–2291 (2006).

    Article  CAS  Google Scholar 

  48. Clipstone, N.A. & Crabtree, G.R. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature 357, 695–697 (1992).

    Article  CAS  Google Scholar 

  49. Vanier, L.E. & Prud'homme, G.J. Cyclosporin A markedly enhances superantigen-induced peripheral T cell deletion and inhibits anergy induction. J. Exp. Med. 176, 37–46 (1992).

    Article  CAS  Google Scholar 

  50. Powell, J.D. et al. Low-dose radiation plus rapamycin promotes long-term bone marrow chimerism. Transplantation 80, 1541–1545 (2005).

    Article  CAS  Google Scholar 

  51. Genot, E.M., Parker, P.J. & Cantrell, D.A. Analysis of the role of protein kinase C-α, -ε, and -ζ in T cell activation. J. Biol. Chem. 270, 9833–9839 (1995).

    Article  CAS  Google Scholar 

  52. Mangues, R. et al. Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice. Cancer Res. 58, 1253–1259 (1998).

    CAS  PubMed  Google Scholar 

  53. Pei, X.Y. et al. The farnesyltransferase inhibitor L744832 potentiates UCN-01-induced apoptosis in human multiple myeloma cells. Clin. Cancer Res. 11, 4589–4600 (2005).

    Article  CAS  Google Scholar 

  54. Lyons, D.S. et al. A TCR binds to antagonist ligands with lower affinities and faster dissociation rates than to agonists. Immunity 5, 53–61 (1996).

    Article  CAS  Google Scholar 

  55. Yokosuka, T. et al. Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat. Immunol. 6, 1253–1262 (2005).

    Article  CAS  Google Scholar 

  56. Zollner, T.M. et al. Proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model. J. Clin. Invest. 109, 671–679 (2002).

    Article  CAS  Google Scholar 

  57. Schwartz, R.H. T cell anergy. Annu. Rev. Immunol. 21, 305–334 (2003).

    Article  CAS  Google Scholar 

  58. Cemerski, S. et al. The stimulatory potency of T cell antigens is influenced by the formation of the immunological synapse. Immunity 26, 345–355 (2007).

    Article  CAS  Google Scholar 

  59. Delon, J., Bercovici, N., Raposo, G., Liblau, R. & Trautmann, A. Antigen-dependent and -independent Ca2+ responses triggered in T cells by dendritic cells compared with B cells. J. Exp. Med. 188, 1473–1484 (1998).

    Article  CAS  Google Scholar 

  60. Croft, M., Duncan, D.D. & Swain, S.L. Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements. J. Exp. Med. 176, 1431–1437 (1992).

    Article  CAS  Google Scholar 

  61. Wright, D.E. et al. Cyclophosphamide/granulocyte colony-stimulating factor causes selective mobilization of bone marrow hematopoietic stem cells into the blood after M phase of the cell cycle. Blood 97, 2278–2285 (2001).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank R. Steinman and R. Schwartz for discussions; H.A. Zebroski for peptide synthesis; E. Besmer, R. Masilamani and E. Market for manuscript preparation; and T. Starr for technical assistance. TCR-transgenic mice expressing the Vβ3Vα11 were provided by L. Denzin (Memorial Sloan Kettering Cancer Institute). Supported by Fondation de Recherche Medicale (D.S.), the Rothchild Foundation (G.S.), the Cancer Research Institute (T.O.C.), a Bernard Levine Fellowship (R.V.), the Medical Scientist Training Program (GM07739 to R.L.L.), the Schering Foundation (T.S.), the National Institutes of Health (M.C.N. and M.L.D.) and the Howard Hughes Medical Institute (M.C.N.).

Author information

Author notes

  1. Guy Shakhar

    Present address: Present address: Department of Immunology, Weizmann Institute of Science, Rehovot, 76100, Israel.,

  2. Michel C Nussenzweig and Michael L Dustin: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Immunology, The Rockefeller University, New York, 10021, New York, USA

    Dimitris Skokos, Randall L Lindquist, Tanja Schwickert & Michel C Nussenzweig

  2. Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.,

    Guy Shakhar, Rajat Varma, Janelle C Waite, Thomas O Cameron & Michael L Dustin

  3. Howard Hughes Medical Institute, The Rockefeller University, New York, 10021, New York, USA

    Michel C Nussenzweig

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Contributions

D.S., design, immunobiology and imaging experiments, analysis, interpretation, coordination and writing; G.S., R.L.L. and T.S., in vivo imaging, analysis and interpretation; R.V., in vitro Ca2+ experiments, analysis and interpretation; J.C.W., in vivo Ca2+ experiments, analysis and interpretation; T.O.C., in vitro migration, analysis and interpretation; and M.C.N. and M.L.D., design, interpretation, coordination and writing.

Corresponding authors

Correspondence to Michel C Nussenzweig or Michael L Dustin.

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Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–9 and Supplementary Methods (PDF 835 kb)

Supplementary Movie 1

Two-photon visualization of T cell motility in a representative lymph node of a CD11c-EYFP mouse injected 6-9 hours earlier with the high-potency construct α-DEC-L98A. Shown is a maximum intensity projection of a 50 μm-thick volume. Antigen-specific AND T cells which express ECFP (pseudo-colored red) move more slowly than non-specific T cells (EGFP, pseudo-colored orange), and are more frequently decelerated on dendritic cells (EYFP, pseudo-colored green). The sequence is repeated with tracks of specific ECFP-AND cells indicated in cyan, and tracks of nonspecific EGFP-T cells shown in magenta. Time elapsed is in seconds. (MOV 8153 kb)

Supplementary Movie 2

A representative lymph node of a mouse similarly treated with the Y97K peptide, visualized as in Supplementary Movie 1. Antigen-specific T cells move as fast as non-specific T cells, and interact similarly with dendritic cells. (MOV 7943 kb)

Supplementary Movie 3

A representative lymph node of a mouse similarly treated with the low-potency peptide T102L, visualized as in Supplementary Movie 1. Antigen-specific T cells move as fast as non-specific T cells, and interact similarly with dendritic cells. (MOV 9353 kb)

Supplementary Movie 4

Calcium signaling and migration on glass supported bilayers. In vitro activated AND T cells were labeled with fura-2 and were imaged every 15 seconds. The images on the left are pseudo-colored ratio images representing fura-2 ratios, such that purple corresponds to a ratio of 0.2 and red corresponds to a ratio of 1.0. The images on the right are generated using Interference Reflection Microscopy (IRM) and the dark areas represent cells making contact with the bilayer substrate. The bilayer in this sequence contains 10 molecules/μm2 of L98A loaded GPI–I-Ek and 300 molecules /μm2 of GPI–ICAM-1. High calcium fluxes are observed as soon as cells make an IRM and that calcium levels are sustained for long periods of time. This movie is a companion to figure 5A. Only the cells making IRMs are quantified. Scale bar equals 10 μm. (MOV 4546 kb)

Supplementary Movie 5

Calcium signaling and migration on glass supported bilayers. This movie was acquired using similar conditions as in movie 3, except that the bilayer contains 10 molecules/μm2 of Y97K loaded GPI–I-Ek and 300 molecules /μm2 of GPI–ICAM-1. Only the cells making IRMs are quantified. Scale bar equals 10 μm. (MOV 4750 kb)

Supplementary Movie 6

Calcium signaling and migration on glass supported bilayers. This movie was acquired using similar conditions as in movie 3, except that the bilayer contains 10 molecules/μm2 of T102L loaded GPI–I-Ek and 300 molecules /μm2 of GPI–ICAM-1. Only the cells making IRMs are quantified. Scale bar equals 10 μm. (MOV 4512 kb)

Supplementary Movie 7

Calcium signaling and migration on glass supported bilayers. This movie was acquired using similar conditions as in movie 3, except that the bilayer contains 50 molecules/μm2 of unloaded GPI–I-Ek and 300 molecules /μm2 of GPI–ICAM-1. Only the cells making IRMs are quantified. Scale bar equals 10 μm. (MOV 6740 kb)

Supplementary Movie 8

Confocal visualization of Ca2+ response in a representative lymph node of a B10BR mouse injected 5 hours earlier with the high-potency construct α-DEC-L98A. Intravital images were acquired between 0 and 2h after cell transfer. Shown is a maximum intensity projection of a 20 μm-thick volume. Blood flow is visualized by Alexa-647 70Kd dextran administration (pseudo-colored blue). Antigen-specific AND T cells labeled with Cell Tracker Orange (CMRA) (pseudo-colored red). Cells were co-labeled with Fluo-4, a calcium sensitive dye (pseudo-colored green). Increases in Fluo-4 fluorescence indicate high Ca2+ levels. Shown here, high Fluo-4 fluorescence intensity occurs as AND T cells exit the blood vessel, appears as yellow/orange when overlapping with the cytoplasmic dye. (AVI 2470 kb)

Supplementary Movie 9

Confocal visualization of Ca2+ response in a representative lymph node of a B10BR mouse injected 5 hours earlier with the medium-potency construct α-DEC-Y97K. As described in Supplementary Movie 8. (AVI 3897 kb)

Supplementary Movie 10

Confocal visualization of Ca2+ response in a representative lymph node of a B10BR mouse injected 5 hours earlier with the low-potency construct α-DEC-T102L. As described in Supplementary Movie 8. (AVI 3939 kb)

Supplementary Movie 11

Confocal visualization of Ca2+ response in a representative lymph node of a B10BR mouse used as untreated control. As described in Supplementary Movie 8. (AVI 5544 kb)

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Skokos, D., Shakhar, G., Varma, R. et al. Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes. Nat Immunol 8, 835–844 (2007). https://doi.org/10.1038/ni1490

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