Blood Journal
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Endogenous galectin-1 enforces class I–restricted TCR functional fate decisions in thymocytes

  1. Scot D. Liu1,
  2. Chan C. Whiting2,
  3. Tamar Tomassian3,
  4. Mabel Pang4,
  5. Stephanie J. Bissel1,
  6. Linda G. Baum4,
  7. Valeri V. Mossine5,
  8. Françoise Poirier6,
  9. Margaret E. Huflejt7, and
  10. M. Carrie Miceli1,3
  1. 1Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles;
  2. 2Ingenuity Systems, Partner & Professional Services, Redwood City, CA;
  3. 3Molecular Biology Institute and
  4. 4Department of Pathology and Laboratory Medicine, University of California, Los Angeles;
  5. 5Department of Biochemistry, University of Missouri, Columbia;
  6. 6Institut Jacques Monod, Centre National de la Recherche Scientifique Unité Mixte de Recherche Universities, Paris, France; and
  7. 7GlycoMedical Research Institute, La Jolla, CA

Abstract

During thymocyte development, the T-cell receptor (TCR) can discriminate major histocompatibility complex (MHC)/peptide ligands over a narrow range of affinities and translate subtle differences into functional fate decisions. How small differences in TCR input are translated into absolute differences in functional output is unclear. We examined the effects of galectin-1 ablation in the context of class-I–restricted thymocyte development. Galectin-1 expression opposed TCR partial agonist-driven positive selection, but promoted TCR agonist-driven negative selection of conventional CD8+ T cells. Galectin-1 expression also promoted TCR agonist-driven CD8αα intestinal intraepithelial lymphocytes (IEL) development. Recombinant galectin-1 enhanced TCR binding to agonist/MHC complexes and promoted a negative-selection-signaling signature, reflected in intensified rapid and transient extracellular signal-regulated kinase (ERK) activation. In contrast, galectin-1 expression antagonized ERK activity in thymocytes undergoing positive selection. We propose that galectin-1 aids in discriminating TCR-directed fate decisions by promoting TCR binding to agonist/MHC complexes and enforcing agonist-driven signals, while opposing partial-agonist signals. In this way, galectin-1 widens the distinction between TCR-directed functional fate cues.

  • Submitted September 20, 2007.
  • Accepted March 4, 2008.
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