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Blood, 1 July 2008, Vol. 112, No. 1, pp. 120-130.
Prepublished online as a Blood First Edition Paper on March 6, 2008; DOI 10.1182/blood-2007-09-114181.
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IMMUNOBIOLOGY
Endogenous galectin-1 enforces class I–restricted TCR functional fate decisions in thymocytes
Scot D. Liu1,
Chan C. Whiting2,
Tamar Tomassian3,
Mabel Pang4,
Stephanie J. Bissel1,
Linda G. Baum4,
Valeri V. Mossine5,
Françoise Poirier6,
Margaret E. Huflejt7, and
M. Carrie Miceli1,3
1 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles;
2 Ingenuity Systems, Partner & Professional Services, Redwood City, CA;
3 Molecular Biology Institute and
4 Department of Pathology and Laboratory Medicine, University of California, Los Angeles;
5 Department of Biochemistry, University of Missouri, Columbia;
6 Institut Jacques Monod, Centre National de la Recherche Scientifique Unité Mixte de Recherche Universities, Paris, France; and
7 GlycoMedical Research Institute, La Jolla, CA
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 CD8 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.

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