Endogenous galectin-1 enforces class I-restricted TCR functional fate decisions in thymocytes.
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 CD8alphaalpha 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.
Liu
Scot D
SD
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095-1570, USA.
Whiting
Chan C
CC
Tomassian
Tamar
T
Pang
Mabel
M
Bissel
Stephanie J
SJ
Baum
Linda G
LG
Mossine
Valeri V
VV
Poirier
Françoise
F
Huflejt
Margaret E
ME
Miceli
M Carrie
MC
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D006182:H-Y Antigen / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D037483:Galectin 1; D006182:H-Y Antigen; D015395:Histocompatibility Antigens Class I; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins