Abstract
Ligand binding to the multichain immune recognition receptors (MIRRs) leads to receptor triggering and subsequent lymphocyte activation. MIRR signal transduction pathways have been extensively studied, but it is still not clear how binding of the ligand to the receptor is initially communicated across the plasma membrane to the cells interior. Models proposed for MIRR triggering can be grouped into three categories. Firstly, ligand binding invokes receptor clustering, resulting in the approximation of kinases to the MIRR and receptor phosphorylation. Secondly, Ugand binding induces a conformational change of the receptor. Thirdly, upon ligand-binding, receptors and kinases are segregated from phosphatases, leading to a net phosphorylation of the receptor. In this review, we focus on the homoclustering induced by multivalent ligands, the heteroclustering induced by simultaneous binding of the ligand to the MIRR and a coreceptor and the pseudodimer model.
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References
Reth M. Antigen receptor tail clue. Nature 1989; 338:383.
Iwashima M, Irving BA, van Oers NS et al. Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. Science 1994; 263(5150):1136–1139.
Rolli V, Gallwitz M, Wossning T et al. Amplification of B-cell antigen receptor signaling by a Syk/ITAM positive feedback loop. Mol Cell 2002; 10(5):1057–1069.
Boniface JJ, Rabinowitz JD, Wülfing C et al. Initiation of signal transduction through the T-cell receptor requires the peptide multivalent engagement of MHC ligands. Immunity 1998; 9:459–466.
Cochran JR, Cameron TO, Stern LJ. The relationship of MHC-peptide binding and T-cell activation probed using chemically defined MHC class II oligomers. Immunity 2000; 12(3):241–250.
Ortega E, Schweitzer-Stenner R, Pecht I. Possible orientational constraints determine secretory signals induced by aggregation of IgE receptors on masT-cells. EMBO J 1988; 7(13):4101–4109.
Erickson J, Kane P, Goldstein B et al. Cross-linking of IgE-receptor complexes at the cell surface:a fluorescence method for studying the binding of monovalent and bivalent haptens to IgE. Mol Immunol 1986; 23(7):769–781.
Kim YM, Pan JY, Korbel GA et al. Monovalent ligation of the B-cell receptor induces receptor activation but fails to promote antigen presentation. Proc Natl Acad Sci USA 2006; 103(9):3327–3332.
Irvine DJ, Purbhoo MA, Krogsgaard M et al. Direct observation of ligand recognition by T-cells. Nature 2002; 419:845–849.
Wülfing C, Sumen C, Sjaastad MD et al. Costimulation and endogenous MHC ligands contribute to T-cell recognition. Nat Immunol 2002; 3:42–47.
Stefanova I, Dorfman JR, Germain RN. Self-recognition promotes the foreign antigen sensitivity of naive T-lymphocytes. Nature 2002; 420(6914):429–434.
Krogsgaard M, Li QJ, Sumen C et al. Agonist/endogenous peptide-MHC heterodimers drive T-cell activation and sensitivity. Nature 2005; 434(7030):238–243.
Chang TW, Kung PC, Gingras SP et al. Does OKT3 monoclonal antibody react with an antigenrecognition structure on human T-cells? Proc Natl Acad Sci USA 1981; 78(3):1805–1808.
Kaye J, Janeway CA Jr. The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T-cell clone blocks activation by either allogeneic la or antigen and self-la. J Exp Med 1984; 159(5):1397–1412.
Ashwell JD, Klausner RD. Genetic and mutational analysis of the T-cell antigen receptor. Annu Rev Immunol 1990; 8:139–167.
Yokosuka T, Sakata-Sogawa K, Kobayashi W et al. Newly generated T-cell receptor microclusters initiate and sustain T-cell activation by recruitment of Zap70 and SLP-76. Nat Immunol 2005; 6(12):1253–1262.
Sigalov A. Multi-chain immime recognition receptors:spatial organization and signal transduction. Semin Immunol 2005; 17(1):51–64.
Dintzis HM, Dintzis RZ, Vogclstein B. Molecular determinants of immunogenicity:the immunon model of immune response. Proc Natl Acad Sci USA 1976; 73(10):3671–3675.
Schamel WW, Reth M. Monomeric and oligomeric complexes of the B-cell antigen receptor. Immunity 2000; 13(1):5–14.
Wilson BS, PfeifFer JR, Oliver JM. Observing FcepsilonRI signaling from the inside of the masT-cell membrane. J Cell Biol 2000; 149(5):1131–1142.
Schamel WW, Arechaga I, Risucno RM et al. Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response. J Exp Med 2005; 202:493–503.
Alarcon B, Swamy M, van Santen HM et al. T-cell antigen-receptor stoichiometry: Preclustering for sensitivity. EMBO Rep 2006; 7(5):490–495.
Rojo JM, Janeway CA Jr. The biological activity of anti-T-cell receptor variable region monoclonal antibodies is determined by the epitope recognized. J Immunol 1988; 140:1081–1088.
Gil D, Schamel WW, Montoya M et al. Recruitment of Nek by CD3 epsilon reveals a ligand-induced conformational change essential for T-cell receptor signaling and synapse formation. Cell 2002; 109(7):901–912.
Minguet S, Swamy M, Alarcon B et al. Full activation of the T-cell antigen receptor requires both clustering and conformational changes at CD3. Immunity 2007; 26(1):43–54.
Schafer PH, Pierce SK, Jardetzky TS. The structure of MHC class II: A role for dimer of dimers. Semin Immunol 1995; 7(6):389–398.
Krishna S, Benaroch P, Pillai S. Tetrameric cell-surface MHC class I molecules. Nature 1992; 357(6374):164–167.
Garboczi DN, Ghosh P, Utz U et al. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 1996; 384(6605):134–141.
Garcia KC, Degano M, Stanfield RL et al. An alphabeta T-cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science 1996; 274(5285):209–219.
Wang JH, Meijers R, Xiong Y et al. Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule. Proc Natl Acad Sci USA 2001; 98(19):10799–10804.
Kim PW, Sun ZY, Blacklow SC et al. A zinc clasp structure tethers Lck to T-cell coreceptors CD4 and CDS. Science 2003; 301(5640): 1725–1728.
Madrenas J, Chau LA, Smith J et al. The efficiency of CD4 recruitment to ligand-engaged TCR controls the agonist/partial agonist properties of peptide-MHC molecule ligands. J Exp Med 1997; 185(2):219–229.
Parnes JR. Molecular biology and frmction of CD4 and CD8. Adv Immunol 1989; 44:265–311.
Viola A, Salio M, Tuosto L et al. Quantitative contribution of CD4 and CD 8 to T-cell antigen receptor serial triggering. J Exp Med 1997; 186(10):1775–1779.
Suzuki S, Kupsch J, Eichmann K et al. Biochemical evidence of the physical association of the majority of CD3 delta chains with the accessory/coreccptor molecules CD4 and CD8 on nonactivated T-lymphocytes. Eur J Immunol 1992; 22(10):2475–2479.
Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 2000; 1(l):31–39.
Xavier R, Brennan T, Li Q e t al. Membrane compartmentation is required for efficient T-cell activation. Immunity 1998; 8:723–732.
Montixi C, Langlet C, Bernard AM et al. Engagement of T-cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains. EMBO J 1998; 17(18):5334–5348.
Field KA, Holowka D, Baird B. Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains. J Biol Chem 1997; 272(7):4276–4280.
Cheng PC, Dykstra ML, Mitchell RN et al. A role for lipid rafts in B-cell antigen receptor signaling and antigen targeting. J Exp Med 1999; 190(11):1549–1560.
Langlet C, Bernard AM, Drevot P et al. Membrane rafts and signaling by the multichain immune recognition receptors. Curr Opin Immunol 2000; 12(3):250–255.
Kabouridis PS, Magee Al, Ley SC. S-acylation of LCK protein tyrosine kinase is essential for its signalling function in T-lymphocytes. EMBO J 1997; 16(16):4983–4998.
Janes PW, Ley SC, Magee AL Aggregation of lipid rafts accompanies signaling via the T-cell antigen receptor. J Cell Biol 1999; 147(2):447–461.
Cheng PC, Brown BK, Song W et al. Translocation of the B-cell antigen receptor into lipid rafts reveals a novel step in signaling. J Immunol 2001; 166(6):3693–3701.
Field KA, Holowka D, Baird B. Structural aspects of the association of FcepsilonRI with detergentresistant membranes. J Biol Chem 1999; 274(3):1753–1758.
Pierce SK. Lipid rafts and B-cell activation. Nat Rev Immunol 2002; 2(2):96–105.
Drevot P, Langlet C, Guo XJ et al. TCR signal initiation machinery is pre-assembled and activated in a subset of membrane rafts. EMBO J 2002; 21(8):1899–1908.
Janes PW, Ley SC, Magee Al et al. The role of lipid rafts in T-cell antigen receptor (TCR) signalling. Semin Immunol 2000; 12(1):23–34.
Cinek T, Hilgert I, Horejsi V. An alternative way of CD4 and CD8 association with protein kinases of the Src family. Immunogenetics 1995; 41 (2-3): 110–116.
Munro S. Lipid rafts: Elusive or illusive? Cell 2003; 115(4):377–388.
Guo B, Kato RM, Garcia-Lloret M et al. Engagement of the human preB-cell receptor generates a lipid raft-dependent calcium signaling complex. Immunity 2000; 13(2):243–253.
Saint-Ruf C, Panigada M, Azogui O et al. Different initiation of preTCR and gammadeltaTCR signalling. Nature 2000; 406(6795):524–527.
Ohnishi K, Melchers F. The nonimmunoglobulin portion of lambda5 mediates cell-autonomous preB-cell receptor signaling. Nat Immunol 2003; 4(9):849–856.
Yamasaki S, Ishikawa E, Sakuma M et al. Mechanistic basis of preT-cell receptor-mediated autonomous signaling critical for thymocyte development. Nat Immunol 2006; 7(1):67–75.
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Schamel, W.W., Reth, M. (2008). Clustering Models. In: Sigalov, A.B. (eds) Multichain Immune Recognition Receptor Signaling. Advances in Experimental Medicine and Biology, vol 640. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09789-3_6
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DOI: https://doi.org/10.1007/978-0-387-09789-3_6
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