1932

Abstract

Cell-cell communication is critical for the development and function of multicellular organisms. A crucial means by which cells communicate with one another is physical interactions between receptors on one cell and their ligands on a neighboring cell. ligand:receptor interactions activate the receptor, ultimately leading to changes in the fate of the receptor-expressing cells. Such signaling is known to be critical for the functions of cells in the nervous and immune systems, among others. Historically, interactions are the primary conceptual framework for understanding cell-cell communication. However, cells often coexpress many receptors and ligands, and a subset of these has been reported to interact in and profoundly impact cell functions. interactions likely constitute a fundamental, understudied regulatory mechanism in cell biology. Here, I discuss how interactions between membrane receptors and ligands regulate immune cell functions, and I also highlight outstanding questions in the field.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cellbio-120420-103941
2023-10-16
2024-04-29
Loading full text...

Full text loading...

/deliver/fulltext/cellbio/39/1/annurev-cellbio-120420-103941.html?itemId=/content/journals/10.1146/annurev-cellbio-120420-103941&mimeType=html&fmt=ahah

Literature Cited

  1. Akira S, Takeda K, Kaisho T. 2001. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2:675–80
    [Google Scholar]
  2. Bachmann MF, Köhler G, Ecabert B, Mak TW, Kopf M. 1999. Cutting edge: lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous. J. Immunol. 163:1128–31
    [Google Scholar]
  3. Bacia K, Schwille P. 2007. Practical guidelines for dual-color fluorescence cross-correlation spectroscopy. Nat. Protoc. 2:2842–56
    [Google Scholar]
  4. Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH. 2016. Coinhibitory pathways in immunotherapy for cancer. Annu. Rev. Immunol. 34:539–73
    [Google Scholar]
  5. Bell JK, Mullen GE, Leifer CA, Mazzoni A, Davies DR, Segal DM. 2003. Leucine-rich repeats and pathogen recognition in Toll-like receptors. Trends Immunol. 24:528–33
    [Google Scholar]
  6. Berezin MY, Achilefu S. 2010. Fluorescence lifetime measurements and biological imaging. Chem. Rev. 110:2641–84
    [Google Scholar]
  7. Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. 2007. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 27:111–22
    [Google Scholar]
  8. Cai E, Marchuk K, Beemiller P, Beppler C, Rubashkin MG et al. 2017. Visualizing dynamic microvillar search and stabilization during ligand detection by T cells. Science 356:aal3118
    [Google Scholar]
  9. Cao E, Ramagopal UA, Fedorov A, Fedorov E, Yan Q et al. 2006. NTB-A receptor crystal structure: insights into homophilic interactions in the signaling lymphocytic activation molecule receptor family. Immunity 25:559–70
    [Google Scholar]
  10. Chaudhri A, Xiao Y, Klee AN, Wang X, Zhu B, Freeman GJ. 2018. PD-L1 binds to B7-1 only in cis on the same cell surface. Cancer Immunol. Res. 6:921–29
    [Google Scholar]
  11. Chen L, Flies DB. 2013. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat. Rev. Immunol. 13:227–42
    [Google Scholar]
  12. Cheung TC, Oborne LM, Steinberg MW, Macauley MG, Fukuyama S et al. 2009. T cell intrinsic heterodimeric complexes between HVEM and BTLA determine receptivity to the surrounding microenvironment. J. Immunol. 183:7286–96
    [Google Scholar]
  13. Collins BE, Blixt O, DeSieno AR, Bovin N, Marth JD, Paulson JC. 2004. Masking of CD22 by cis ligands does not prevent redistribution of CD22 to sites of cell contact. PNAS 101:6104–9
    [Google Scholar]
  14. Davis DM. 2007. Intercellular transfer of cell-surface proteins is common and can affect many stages of an immune response. Nat. Rev. Immunol. 7:238–43
    [Google Scholar]
  15. Davis SJ, van der Merwe PA. 2006. The kinetic-segregation model: TCR triggering and beyond. Nat. Immunol. 7:803–9
    [Google Scholar]
  16. Demetriou P, Abu-Shah E, Valvo S, McCuaig S, Mayya V et al. 2020. A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals. Nat. Immunol. 21:1232–43
    [Google Scholar]
  17. Dobbins J, Gagnon E, Godec J, Pyrdol J, Vignali DAA et al. 2016. Binding of the cytoplasmic domain of CD28 to the plasma membrane inhibits Lck recruitment and signaling. Sci. Signal. 9:ra75
    [Google Scholar]
  18. Doucey MA, Scarpellino L, Zimmer J, Guillaume P, Luescher IF et al. 2004. Cis association of Ly49A with MHC class I restricts natural killer cell inhibition. Nat. Immunol. 5:328–36
    [Google Scholar]
  19. Dustin ML. 2014. The immunological synapse. Cancer Immunol. Res. 2:1023–33
    [Google Scholar]
  20. Engel P, Eck MJ, Terhorst C. 2003. The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease. Nat. Rev. Immunol. 3:813–21
    [Google Scholar]
  21. Evans EJ, Esnouf RM, Manso-Sancho R, Gilbert RJ, James JR et al. 2005. Crystal structure of a soluble CD28-Fab complex. Nat. Immunol. 6:271–79
    [Google Scholar]
  22. Farhat K, Riekenberg S, Heine H, Debarry J, Lang R et al. 2008. Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling. J. Leukoc. Biol. 83:692–701
    [Google Scholar]
  23. Ghosh S, Di Bartolo V, Tubul L, Shimoni E, Kartvelishvily E et al. 2020. ERM-dependent assembly of T cell receptor signaling and co-stimulatory molecules on microvilli prior to activation. Cell Rep. 30:3434–47.e6
    [Google Scholar]
  24. Griffiths GM, Tsun A, Stinchcombe JC. 2010. The immunological synapse: a focal point for endocytosis and exocytosis. J. Cell Biol. 189:399–406
    [Google Scholar]
  25. Haile ST, Bosch JJ, Agu NI, Zeender AM, Somasundaram P et al. 2011. Tumor cell programmed death ligand 1-mediated T cell suppression is overcome by coexpression of CD80. J. Immunol. 186:6822–29
    [Google Scholar]
  26. Ikemizu S, Gilbert RJ, Fennelly JA, Collins AV, Harlos K et al. 2000. Structure and dimerization of a soluble form of B7-1. Immunity 12:51–60
    [Google Scholar]
  27. Johnston RJ, Comps-Agrar L, Hackney J, Yu X, Huseni M et al. 2014. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell 26:923–37
    [Google Scholar]
  28. Joly E, Hudrisier D. 2003. What is trogocytosis and what is its purpose?. Nat. Immunol. 4:815
    [Google Scholar]
  29. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. 2008. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 26:677–704
    [Google Scholar]
  30. Kobayashi E, Jin A, Hamana H, Shitaoka K, Tajiri K et al. 2022. Rapid cloning of antigen-specific T-cell receptors by leveraging the cis activation of T cells. Nat. Biomed. Eng. 6:806–18
    [Google Scholar]
  31. Lakowicz JR. 1999. Principles of Fluorescence Spectroscopy New York: Springer. , 2nd ed..
  32. Li B, Lu Y, Zhong MC, Qian J, Li R et al. 2022. Cis interactions between CD2 and its ligands on T cells are required for T cell activation. Sci. Immunol. 7:eabn6373
    [Google Scholar]
  33. Lin DY, Tanaka Y, Iwasaki M, Gittis AG, Su HP et al. 2008. The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. PNAS 105:3011–16
    [Google Scholar]
  34. Masuda A, Nakamura A, Maeda T, Sakamoto Y, Takai T. 2007. Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation. J. Exp. Med. 204:907–20
    [Google Scholar]
  35. Maurer MF, Lewis KE, Kuijper JL, Ardourel D, Gudgeon CJ et al. 2022. The engineered CD80 variant fusion therapeutic davoceticept combines checkpoint antagonism with conditional CD28 costimulation for anti-tumor immunity. Nat. Commun. 13:1790
    [Google Scholar]
  36. McArdel SL, Terhorst C, Sharpe AH. 2016. Roles of CD48 in regulating immunity and tolerance. Clin. Immunol. 164:10–20
    [Google Scholar]
  37. Medzhitov R. 2001. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1:135–45
    [Google Scholar]
  38. Mitchison NA. 2004. T-cell–B-cell cooperation. Nat. Rev. Immunol. 4:308–12
    [Google Scholar]
  39. Muhammad A, Schiller HB, Forster F, Eckerstorfer P, Geyeregger R et al. 2009. Sequential cooperation of CD2 and CD48 in the buildup of the early TCR signalosome. J. Immunol. 182:7672–80
    [Google Scholar]
  40. Nakada-Tsukui K, Nozaki T. 2021. Trogocytosis in unicellular eukaryotes. Cells 10:112975
    [Google Scholar]
  41. Nandagopal N, Santat LA, Elowitz MB. 2019. Cis-activation in the Notch signaling pathway. eLife 8:e37880
    [Google Scholar]
  42. Neefjes J, Jongsma ML, Paul P, Bakke O. 2011. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat. Rev. Immunol. 11:823–36
    [Google Scholar]
  43. Oh SA, Wu DC, Cheung J, Navarro A, Xiong H et al. 2020. PD-L1 expression by dendritic cells is a key regulator of T-cell immunity in cancer. Nat. Cancer 1:681–91
    [Google Scholar]
  44. Orange JS. 2008. Formation and function of the lytic NK-cell immunological synapse. Nat. Rev. Immunol. 8:713–25
    [Google Scholar]
  45. Orbach R, Su X. 2020. Surfing on membrane waves: microvilli, curved membranes, and immune signaling. Front. Immunol. 11:2187
    [Google Scholar]
  46. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD et al. 2000. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. PNAS 97:13766–71
    [Google Scholar]
  47. Razi N, Varki A. 1998. Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec-2) on B lymphocytes. PNAS 95:7469–74
    [Google Scholar]
  48. Razvag Y, Neve-Oz Y, Sajman J, Reches M, Sherman E. 2018. Nanoscale kinetic segregation of TCR and CD45 in engaged microvilli facilitates early T cell activation. Nat. Commun. 9:732
    [Google Scholar]
  49. Saggu G, Okubo K, Chen Y, Vattepu R, Tsuboi N et al. 2018. Cis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 limits antibody-mediated neutrophil recruitment. Nat. Commun. 9:5058
    [Google Scholar]
  50. Schwille P, Meyer-Almes FJ, Rigler R. 1997. Dual-color fluorescence cross-correlation spectroscopy for multicomponent diffusional analysis in solution. Biophys. J. 72:1878–86
    [Google Scholar]
  51. Sorkin A, von Zastrow M. 2009. Endocytosis and signalling: intertwining molecular networks. Nat. Rev. Mol. Cell Biol. 10:609–22
    [Google Scholar]
  52. Stamper CC, Zhang Y, Tobin JF, Erbe DV, Ikemizu S et al. 2001. Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature 410:608–11
    [Google Scholar]
  53. Stephan MT, Ponomarev V, Brentjens RJ, Chang AH, Dobrenkov KV et al. 2007. T cell–encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nat. Med. 13:1440–49
    [Google Scholar]
  54. Strömqvist J, Johansson S, Xu L, Ohsugi Y, Andersson K et al. 2011. A modified FCCS procedure applied to Ly49A-MHC class I cis-interaction studies in cell membranes. Biophys. J. 101:1257–69
    [Google Scholar]
  55. Sugiura D, Maruhashi T, Okazaki IM, Shimizu K, Maeda TK et al. 2019. Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses. Science 364:558–66
    [Google Scholar]
  56. Waldman AD, Fritz JM, Lenardo MJ. 2020. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20:651–68
    [Google Scholar]
  57. Xu X, Dennett P, Zhang J, Sherrard A, Zhao Y et al. 2023. CTLA4 depletes T cell endogenous and trogocytosed B7 ligands via cis-endocytosis. J. Exp. Med. 220:e20221391
    [Google Scholar]
  58. Zenke S, Sica MP, Steinberg F, Braun J, Zink A et al. 2022. Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation. Nat. Commun. 13:6459
    [Google Scholar]
  59. Zhao Y, Caron C, Chan YY, Lee CK, Xu X et al. 2023. Cis-B7:CD28 interactions at invaginated synaptic membranes activate CD28 and promote T cell function and anti-tumor immunity. Immunity 56:1187–203.e12
    [Google Scholar]
  60. Zhao Y, Harrison DL, Song Y, Ji J, Huang J, Hui E 2018. Antigen-presenting cell-intrinsic PD-1 neutralizes PD-L1 in cis to attenuate PD-1 signaling in T cells. Cell Rep. 24:379–90.e6
    [Google Scholar]
  61. Zhao Y, Lee CK, Lin CH, Gassen RB, Xu X et al. 2019. PD-L1:CD80 cis-heterodimer triggers the co-stimulatory receptor CD28 while repressing the inhibitory PD-1 and CTLA-4 pathways. Immunity 51:1059–73.e9
    [Google Scholar]
/content/journals/10.1146/annurev-cellbio-120420-103941
Loading
/content/journals/10.1146/annurev-cellbio-120420-103941
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error