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N-glycosylation bidirectionally extends the boundaries of thymocyte positive selection by decoupling Lck from Ca²âº signaling.
Zhou, Raymond W; Mkhikian, Haik; Grigorian, Ani; Hong, Amanda; Chen, David; Arakelyan, Araz; Demetriou, Michael.
Affiliation
  • Zhou RW; 1] Department of Neurology, University of California, Irvine, Irvine, California, USA. [2] Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA. [3] Institute for Immunology, University of California, Irvine, Irvine, California, USA.
  • Mkhikian H; 1] Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA. [2] Institute for Immunology, University of California, Irvine, Irvine, California, USA.
  • Grigorian A; 1] Department of Neurology, University of California, Irvine, Irvine, California, USA. [2] Institute for Immunology, University of California, Irvine, Irvine, California, USA.
  • Hong A; Department of Neurology, University of California, Irvine, Irvine, California, USA.
  • Chen D; Department of Neurology, University of California, Irvine, Irvine, California, USA.
  • Arakelyan A; Department of Neurology, University of California, Irvine, Irvine, California, USA.
  • Demetriou M; 1] Department of Neurology, University of California, Irvine, Irvine, California, USA. [2] Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA. [3] Institute for Immunology, University of California, Irvine, Irvine, California, USA.
Nat Immunol ; 15(11): 1038-45, 2014 Nov.
Article in En | MEDLINE | ID: mdl-25263124
ABSTRACT
Positive selection of diverse yet self-tolerant thymocytes is vital to immunity and requires a limited degree of T cell antigen receptor (TCR) signaling in response to self peptide-major histocompatibility complexes (self peptide-MHCs). Affinity of newly generated TCR for peptide-MHC primarily sets the boundaries for positive selection. We report that N-glycan branching of TCR and the CD4 and CD8 coreceptors separately altered the upper and lower affinity boundaries from which interactions between peptide-MHC and TCR positively select T cells. During thymocyte development, N-glycan branching varied approximately 15-fold. N-glycan branching was required for positive selection and decoupled Lck signaling from TCR-driven Ca(2+) flux to simultaneously promote low-affinity peptide-MHC responses while inhibiting high-affinity ones. Therefore, N-glycan branching imposes a sliding scale on interactions between peptide-MHC and TCR that bidirectionally expands the affinity range for positive selection.
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Full text: 1 Database: MEDLINE Main subject: Polysaccharides / Receptors, Antigen, T-Cell / Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Calcium Signaling / Thymocytes Limits: Animals Language: En Year: 2014 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Polysaccharides / Receptors, Antigen, T-Cell / Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Calcium Signaling / Thymocytes Limits: Animals Language: En Year: 2014 Type: Article