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Filipp D, Ballek O, Manning J. Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement. Front Immunol. 2012;3:155doi: 10.3389/fimmu.2012.00155.
Filipp, D., Ballek, O., & Manning, J. (2012). Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement. Frontiers in immunology, 3155. https://doi.org/10.3389/fimmu.2012.00155
Filipp, Dominik, et al. "Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement." Frontiers in immunology vol. 3 (2012): 155. doi: https://doi.org/10.3389/fimmu.2012.00155
Filipp D, Ballek O, Manning J. Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement. Front Immunol. 2012 Jun 12;3:155. doi: 10.3389/fimmu.2012.00155. eCollection 2012. PMID: 22701458; PMCID: PMC3372939.
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Front Immunol. 2012 Jun 12;3:155. doi: 10.3389/fimmu.2012.00155. eCollection 2012.

Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement.

Frontiers in immunology

Dominik Filipp, Ondrej Ballek, Jasper Manning

Affiliations

  1. Laboratory of Immunobiology, Institute of Molecular Genetics AS CR Prague, Czech Republic.

PMID: 22701458 PMCID: PMC3372939 DOI: 10.3389/fimmu.2012.00155

Abstract

In spite of a comprehensive understanding of the schematics of T cell receptor (TCR) signaling, the mechanisms regulating compartmentalization of signaling molecules, their transient interactions, and rearrangement of membrane structures initiated upon TCR engagement remain an outstanding problem. These gaps in our knowledge are exemplified by recent data demonstrating that TCR triggering is largely dependent on a preactivated pool of Lck concentrated in T cells in a specific type of membrane microdomains. Our current model posits that in resting T cells all critical components of TCR triggering machinery including TCR/CD3, Lck, Fyn, CD45, PAG, and LAT are associated with distinct types of lipid-based microdomains which represent the smallest structural and functional units of membrane confinement able to negatively control enzymatic activities and substrate availability that is required for the initiation of TCR signaling. In addition, the microdomains based segregation spatially limits the interaction of components of TCR triggering machinery prior to the onset of TCR signaling and allows their rapid communication and signal amplification after TCR engagement, via the process of their coalescence. Microdomains mediated compartmentalization thus represents an essential membrane organizing principle in resting T cells. The integration of these structural and functional aspects of signaling into a unified model of TCR triggering will require a deeper understanding of membrane biology, novel interdisciplinary approaches and the generation of specific reagents. We believe that the fully integrated model of TCR signaling must be based on membrane structural network which provides a proper environment for regulatory processes controlling TCR triggering.

Keywords: Fyn; Lck; TCR triggering; compartmentalization; heavy and light DRMs; membrane microdomains; spatio-temporal regulation

References

  1. Immunol Lett. 1999 Mar 15;67(1):31-9 - PubMed
  2. Immunity. 1996 Nov;5(5):417-28 - PubMed
  3. Nature. 2000 Apr 27;404(6781):999-1003 - PubMed
  4. Immunity. 2007 Jan;26(1):43-54 - PubMed
  5. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395-9 - PubMed
  6. J Virol. 1988 Dec;62(12):4673-9 - PubMed
  7. Nat Rev Immunol. 2007 Feb;7(2):131-43 - PubMed
  8. Prog Lipid Res. 2010 Oct;49(4):390-406 - PubMed
  9. J Mol Graph Model. 2004 Oct;23(2):189-98 - PubMed
  10. Cell Commun Signal. 2011 Dec 08;9(1):31 - PubMed
  11. Eur J Immunol. 1992 May;22(5):1173-8 - PubMed
  12. Immunol Rev. 2003 Feb;191:107-18 - PubMed
  13. J Immunol. 1997 Jun 15;158(12):5773-82 - PubMed
  14. J Immunol. 2002 Nov 1;169(9):5036-42 - PubMed
  15. J Allergy Clin Immunol. 2002 May;109(5):758-70 - PubMed
  16. J Exp Med. 1998 May 18;187(10):1699-709 - PubMed
  17. Cold Spring Harb Perspect Biol. 2010 Apr;2(4):a005140 - PubMed
  18. Nat Rev Immunol. 2008 Sep;8(9):699-712 - PubMed
  19. Nat Immunol. 2006 Nov;7(11):1139-42 - PubMed
  20. Eur J Immunol. 1994 Apr;24(4):959-66 - PubMed
  21. Mol Cell Biol. 2007 Mar;27(5):1960-73 - PubMed
  22. Biochem J. 2004 May 15;380(Pt 1):219-30 - PubMed
  23. J Biol Chem. 2004 Feb 27;279(9):7530-6 - PubMed
  24. Oncogene. 1990 Jun;5(6):803-8 - PubMed
  25. Cell. 2008 Nov 14;135(4):594-6 - PubMed
  26. Blood. 2007 Jul 15;110(2):596-615 - PubMed
  27. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13964-9 - PubMed
  28. J Biol Chem. 2011 Sep 16;286(37):31993-2001 - PubMed
  29. J Biol Chem. 2008 Dec 19;283(51):35815-24 - PubMed
  30. J Biol Chem. 1997 Oct 10;272(41):25429-32 - PubMed
  31. Int Immunol. 2007 Apr;19(4):487-95 - PubMed
  32. Nat Rev Immunol. 2007 Nov;7(11):889-96 - PubMed
  33. Trends Biochem Sci. 2005 Aug;30(8):430-6 - PubMed
  34. Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):E336-42 - PubMed
  35. Cell Immunol. 1997 Jan 10;175(1):1-11 - PubMed
  36. EMBO J. 2002 Apr 15;21(8):1899-908 - PubMed
  37. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8959-63 - PubMed
  38. Nat Immunol. 2011 Jun 05;12(7):655-62 - PubMed
  39. Semin Immunol. 2005 Feb;17(1):3-21 - PubMed
  40. Oncogene. 2004 Oct 18;23(48):7918-27 - PubMed
  41. Biochem J. 2003 Apr 1;371(Pt 1):15-27 - PubMed
  42. J Biol Chem. 2007 Dec 7;282(49):36000-9 - PubMed
  43. Biochimie. 2007 Feb;89(2):192-6 - PubMed
  44. Blood. 2011 Jan 6;117(1):108-17 - PubMed
  45. Cell. 1992 Aug 21;70(4):585-93 - PubMed
  46. Immunity. 2007 Sep;27(3):425-37 - PubMed
  47. Annu Rev Immunol. 2009;27:591-619 - PubMed
  48. Trends Immunol. 2004 Jun;25(6):323-7 - PubMed
  49. Proc Natl Acad Sci U S A. 2003 May 13;100(10):5795-800 - PubMed
  50. Immunol Lett. 2004 Jan 30;91(1):3-9 - PubMed
  51. Immunity. 2007 Nov;27(5):735-50 - PubMed
  52. Mol Immunol. 2004 Jul;41(6-7):645-56 - PubMed
  53. Cold Spring Harb Perspect Biol. 2011 Oct 01;3(10):a004697 - PubMed
  54. Blood. 2006 Jan 1;107(1):213-21 - PubMed
  55. Trends Immunol. 2011 Jan;32(1):1-5 - PubMed
  56. Sci STKE. 2006 Oct 31;2006(359):re14 - PubMed
  57. Nat Immunol. 2006 Aug;7(8):803-9 - PubMed
  58. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6302-6 - PubMed
  59. Science. 2002 Feb 22;295(5559):1539-42 - PubMed
  60. Immunity. 2001 Jun;14(6):669-80 - PubMed
  61. Annu Rev Biophys Biomol Struct. 2003;32:257-83 - PubMed
  62. Cell. 2003 Nov 14;115(4):377-88 - PubMed
  63. Mol Cell Biol. 1999 Jun;19(6):4200-8 - PubMed
  64. J Immunol. 2010 Apr 1;184(7):3689-96 - PubMed
  65. Exp Mol Med. 2000 Mar 31;32(1):18-22 - PubMed
  66. Cell. 2004 Feb 20;116(4):577-89 - PubMed
  67. Biochim Biophys Acta. 2011 Feb;1813(2):367-76 - PubMed
  68. Trends Immunol. 2005 Feb;26(2):97-103 - PubMed
  69. Mol Cell Biol. 2005 Dec;25(23):10533-42 - PubMed
  70. Immunol Rev. 2003 Feb;191:148-64 - PubMed
  71. J Exp Med. 2005 Feb 7;201(3):441-52 - PubMed
  72. Nature. 2002 Oct 24;419(6909):845-9 - PubMed
  73. J Immunol. 2002 May 1;168(9):4480-7 - PubMed
  74. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358-62 - PubMed
  75. Cell. 1992 Feb 7;68(3):533-44 - PubMed
  76. Curr Opin Immunol. 2001 Jun;13(3):299-306 - PubMed
  77. Physiology (Bethesda). 2006 Dec;21:430-9 - PubMed
  78. Biophys J. 2008 Feb 15;94(4):1326-40 - PubMed
  79. J Immunol. 1999 Feb 15;162(4):1879-83 - PubMed
  80. FEBS Lett. 2001 Oct 26;507(2):133-6 - PubMed
  81. EMBO J. 1999 Dec 15;18(24):6917-26 - PubMed
  82. Science. 2011 Nov 25;334(6059):1046-7 - PubMed
  83. Sci Signal. 2011 Sep 13;4(190):ra59 - PubMed
  84. Prog Lipid Res. 2006 May;45(3):187-202 - PubMed
  85. Nature. 1997 Feb 13;385(6617):602-9 - PubMed
  86. Immunol Lett. 2012 Feb 29;142(1-2):64-74 - PubMed
  87. J Exp Med. 2006 Feb 20;203(2):281-7 - PubMed
  88. Oncogene. 2004 Oct 18;23(48):7990-8000 - PubMed
  89. Immunol Today. 1999 Sep;20(9):412-6 - PubMed
  90. Immunity. 1999 Mar;10(3):323-32 - PubMed
  91. Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14859-64 - PubMed
  92. Arch Biochem Biophys. 2005 Feb 1;434(1):150-8 - PubMed
  93. Biochem J. 2004 Aug 1;381(Pt 3):919-28 - PubMed
  94. J Immunol. 2004 Nov 1;173(9):5392-7 - PubMed
  95. Nature. 1996 Dec 5;384(6608):484-9 - PubMed
  96. Mol Membr Biol. 2006 Jan-Feb;23(1):49-57 - PubMed
  97. Cell. 2010 Sep 3;142(5):669-71 - PubMed
  98. Nat Rev Immunol. 2010 Jan;10(1):59-71 - PubMed
  99. Mol Cell Biol. 2000 Feb;20(4):1426-35 - PubMed
  100. Immunol Rev. 2009 Mar;228(1):9-22 - PubMed
  101. Mol Cell Biol. 2006 Nov;26(21):7892-900 - PubMed
  102. Nat Rev Immunol. 2005 Jul;5(7):532-45 - PubMed
  103. Eur J Immunol. 2007 Sep;37(9):2539-48 - PubMed
  104. Mol Membr Biol. 2006 Jan-Feb;23(1):59-69 - PubMed
  105. Biochemistry (Mosc). 2007 Nov;72(11):1216-24 - PubMed
  106. Semin Immunol. 2007 Aug;19(4):255-61 - PubMed
  107. J Biol Chem. 2001 Jun 22;276(25):23173-8 - PubMed
  108. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16916-21 - PubMed
  109. Curr Biol. 1997 May 1;7(5):R295-8 - PubMed
  110. J Immunol. 2009 Feb 15;182(4):2160-7 - PubMed
  111. J Biol Chem. 2010 May 7;285(19):14737-46 - PubMed
  112. Cell. 2008 Nov 14;135(4):702-13 - PubMed
  113. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9 - PubMed
  114. EMBO J. 1997 Aug 15;16(16):4983-98 - PubMed
  115. Science. 1998 Jul 24;281(5376):572-5 - PubMed
  116. FEBS J. 2010 Nov;277(21):4383-97 - PubMed
  117. Nature. 1997 Feb 13;385(6617):595-602 - PubMed
  118. Blood. 2001 Sep 1;98(5):1489-97 - PubMed
  119. Annu Rev Immunol. 2008;26:233-59 - PubMed
  120. J Exp Med. 2000 May 1;191(9):1591-604 - PubMed
  121. Immunity. 2011 Nov 23;35(5):705-20 - PubMed
  122. Annu Rev Immunol. 2003;21:457-81 - PubMed
  123. Nature. 1991 Mar 7;350(6313):62-6 - PubMed
  124. Annu Rev Immunol. 2003;21:107-37 - PubMed
  125. Nat Protoc. 2007;2(9):2159-65 - PubMed
  126. Science. 2010 Jan 1;327(5961):46-50 - PubMed
  127. Exp Cell Res. 2009 Oct 15;315(17):2871-8 - PubMed
  128. Annu Rev Immunol. 2002;20:669-707 - PubMed
  129. J Immunol. 1998 Nov 15;161(10):5491-9 - PubMed
  130. Cell. 2002 Dec 27;111(7):967-79 - PubMed
  131. Mol Cell Biol. 2003 Mar;23(6):2017-28 - PubMed
  132. EMBO J. 1994 Apr 15;13(8):1920-9 - PubMed
  133. Self Nonself. 2010 Jan;1(1):4-39 - PubMed
  134. J Immunol. 1999 Aug 15;163(4):1853-8 - PubMed
  135. Biophys J. 1997 May;72(5):2014-31 - PubMed
  136. J Exp Med. 1998 Nov 2;188(9):1575-86 - PubMed
  137. J Biol Chem. 2008 Sep 26;283(39):26409-22 - PubMed
  138. Nature. 1997 Feb 13;385(6617):650-3 - PubMed
  139. Methods Mol Biol. 2007;398:9-20 - PubMed
  140. Nat Immunol. 2003 Feb;4(2):189-97 - PubMed
  141. J Immunol. 2005 Dec 15;175(12):7947-56 - PubMed
  142. Commun Integr Biol. 2009 Sep;2(5):420-1 - PubMed
  143. Biochem J. 2009 Jan 15;417(2):525-33 - PubMed
  144. Curr Opin Immunol. 2002 Jun;14(3):299-305 - PubMed
  145. Cell. 2008 Dec 12;135(6):1085-97 - PubMed
  146. Immunity. 2010 Jun 25;32(6):766-77 - PubMed
  147. J Exp Med. 1996 Mar 1;183(3):1053-62 - PubMed
  148. Mol Cell Biol. 1993 Mar;13(3):1651-6 - PubMed
  149. Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2): - PubMed
  150. Nat Rev Immunol. 2009 Aug;9(8):543-55 - PubMed
  151. PLoS Comput Biol. 2011 Aug;7(8):e1002076 - PubMed
  152. J Biol Chem. 2010 Apr 9;285(15):11392-401 - PubMed
  153. Nature. 1997 Jun 5;387(6633):569-72 - PubMed
  154. Nature. 1992 Jul 23;358(6384):328-31 - PubMed
  155. Nat Cell Biol. 2006 Nov;8(11):1270-6 - PubMed
  156. J Immunol. 2004 Apr 1;172(7):4266-74 - PubMed
  157. Sci Signal. 2011 Jan 25;4(157):jc2 - PubMed
  158. J Exp Med. 2003 May 5;197(9):1221-7 - PubMed
  159. Annu Rev Immunol. 1994;12:85-116 - PubMed
  160. Cell. 2010 Sep 3;142(5):668-9 - PubMed
  161. J Cell Sci. 2009 May 15;122(Pt 10):1584-94 - PubMed

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