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*
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland;
Centre d’Immunologie, Institut National Scientifique et Recherche Medical-Centre National de Research Scientifique de Marseille-Luminy, Marseille, France; and
Basel Institute for Immunology, Basel, Switzerland
<. >
To investigate the molecular basis that makes heterodimeric
CD8
ß a more efficient coreceptor than homodimeric CD8, we
used various CD8 transfectants of T1.4 T cell hybridomas, which are
specific for H-2Kd, and a photoreactive derivative of the
Plasmodium berghei circumsporozoite
peptide PbCS 252–260 (SYIPSAEKI). We demonstrate that CD8 is
palmitoylated at the cytoplasmic tail of CD8ß and that this allows
partitioning of CD8ß, but not of CD8, in lipid rafts.
Localization of CD8 in rafts is crucial for its coreceptor function.
First, association of CD8 with the src kinase
p56lck takes place nearly exclusively in rafts,
mainly due to increased concentration of both components in this
compartment. Deletion of the cytoplasmic domain of CD8ß abrogated
localization of CD8 in rafts and association with
p56lck. Second, CD8-mediated cross-linking of
p56lck by multimeric Kd-peptide
complexes or by anti-CD8 Ab results in
p56lck activation in rafts, from which the
abundant phosphatase CD45 is excluded. Third, CD8-associated activated
p56lck phosphorylates CD3
in rafts and hence
induces TCR signaling and T cell activation. This study shows that
palmitoylation of CD8ß is required for efficient CD8 coreceptor
function, mainly because it dramatically increases CD8 association with
p56lck and CD8-mediated activation of
p56lck in lipid rafts.
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M. Foti, M.-A. Phelouzat, A. Holm, B. J. Rasmusson, and J.-L. Carpentier p56Lck anchors CD4 to distinct microdomains on microvilli PNAS, February 19, 2002; 99(4): 2008 - 2013. [Abstract] [Full Text] [PDF]
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A. Arcaro, C. Gregoire, T. R. Bakker, L. Baldi, M. Jordan, L. Goffin, N. Boucheron, F. Wurm, P. A. van der Merwe, B. Malissen, et al. CD8{beta} Endows CD8 with Efficient Coreceptor Function by Coupling T Cell Receptor/CD3 to Raft-associated CD8/p56lck Complexes J. Exp. Med., November 19, 2001; 194(10): 1485 - 1495. [Abstract] [Full Text] [PDF]
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A. G. Cawthon, H. Lu, and M. A. Alexander-Miller Peptide Requirement for CTL Activation Reflects the Sensitivity to CD3 Engagement: Correlation with CD8{alpha}{beta} Versus CD8{alpha}{alpha} Expression J. Immunol., September 1, 2001; 167(5): 2577 - 2584. [Abstract] [Full Text] [PDF]
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D. R. Drake III and T. J. Braciale Cutting Edge: Lipid Raft Integrity Affects the Efficiency of MHC Class I Tetramer Binding and Cell Surface TCR Arrangement on CD8+ T Cells J. Immunol., June 15, 2001; 166(12): 7009 - 7013. [Abstract] [Full Text] [PDF]
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M. Higuchi, K. M. Izumi, and E. Kieff Epstein-Barr virus latent-infection membrane proteins are palmitoylated and raft-associated: Protein 1 binds to the cytoskeleton through TNF receptor cytoplasmic factors PNAS, April 10, 2001; 98(8): 4675 - 4680. [Abstract] [Full Text] [PDF]
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T. Harder and M. Kuhn Selective Accumulation of Raft-associated Membrane Protein LAT in T Cell Receptor Signaling Assemblies J. Cell Biol., October 9, 2000; 151(2): 199 - 208. [Abstract] [Full Text] [PDF]
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