| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Chain Phosphorylation and Antagonizes Processive TCR Signal Transduction1
,
Departments of
*
Biological Chemistry and
Microbiology and Immunology, and the
Molecular Biology Institute, University of California School of Medicine, Los Angeles, CA 90095
Galectin-1 is an endogenous lectin with known T cell
immunoregulatory activity, though the molecular basis by which
galectin-1 influences Ag specific T cell responses has not been
elucidated. Here, we characterize the ability of galectin-1 to modulate
TCR signals and responses by T cells with well defined hierarchies of
threshold requirements for signaling distinct functional responses. We
demonstrate that galectin-1 antagonizes TCR responses known to require
costimulation and processive protein tyrosine phosphorylation, such as
IL-2 production, but is permissive for TCR responses that only require
partial TCR signals, such as IFN-
production, CD69 up-regulation,
and apoptosis. Galectin-1 binding alone or together with Ag stimulation
induces partial phosphorylation of TCR-
and the generation of
inhibitory pp21. Galectin-1 antagonizes Ag induced signals and
TCR/costimulator dependent lipid raft clustering at the TCR contact
site. We propose that galectin-1 functions as a T cell
"counterstimulator" to limit required protein segregation and lipid
raft reorganization at the TCR contact site and, thus, processive and
sustained TCR signal transduction. These findings support the concept
that TCR antagonism can arise from the generation of an inhibitory
pp21-based TCR signaling complex. Moreover, they demonstrate that
TCR antagonism can result from T cell interactions with a ligand other
than peptide/MHC.
This article has been cited by other articles:
|
|
 |
|
  S. D. Liu, T. Tomassian, K. W. Bruhn, J. F. Miller, F. Poirier, and M. C. Miceli Galectin-1 Tunes TCR Binding and Signal Transduction to Regulate CD8 Burst Size J. Immunol., May 1, 2009; 182(9): 5283 - 5295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Perone, S. Bertera, W. J. Shufesky, S. J. Divito, A. Montecalvo, A. R. Mathers, A. T. Larregina, M. Pang, N. Seth, K. W. Wucherpfennig, et al. Suppression of Autoimmune Diabetes by Soluble Galectin-1 J. Immunol., March 1, 2009; 182(5): 2641 - 2653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mahajan, T. Madan, N. Kamal, V. K. Singh, R. B. Sim, S. D. Telang, C. N. Ramchand, P. Waters, U. Kishore, and P. U. Sarma Recombinant surfactant protein-D selectively increases apoptosis in eosinophils of allergic asthmatics and enhances uptake of apoptotic eosinophils by macrophages Int. Immunol., August 1, 2008; 20(8): 993 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Liu, C. C. Whiting, T. Tomassian, M. Pang, S. J. Bissel, L. G. Baum, V. V. Mossine, F. Poirier, M. E. Huflejt, and M. C. Miceli Endogenous galectin-1 enforces class I-restricted TCR functional fate decisions in thymocytes Blood, July 1, 2008; 112(1): 120 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Demers, K. Biron-Pain, J. Hebert, A. Lamarre, T. Magnaldo, and Y. St-Pierre Galectin-7 in Lymphoma: Elevated Expression in Human Lymphoid Malignancies and Decreased Lymphoma Dissemination by Antisense Strategies in Experimental Model Cancer Res., March 15, 2007; 67(6): 2824 - 2829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Garin, C.-C. Chu, D. Golshayan, E. Cernuda-Morollon, R. Wait, and R. I. Lechler Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells Blood, March 1, 2007; 109(5): 2058 - 2065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Meraner, V. Horejsi, A. Wolpl, G. F. Fischer, G. Stingl, and D. Maurer Dendritic Cells Sensitize TCRs through Self-MHC-Mediated Src Family Kinase Activation J. Immunol., February 15, 2007; 178(4): 2262 - 2271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Barrionuevo, M. Beigier-Bompadre, J. M. Ilarregui, M. A. Toscano, G. A. Bianco, M. A. Isturiz, and G. A. Rabinovich A Novel Function for Galectin-1 at the Crossroad of Innate and Adaptive Immunity: Galectin-1 Regulates Monocyte/Macrophage Physiology through a Nonapoptotic ERK-Dependent Pathway J. Immunol., January 1, 2007; 178(1): 436 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Walzel, A. A. Fahmi, M. A. Eldesouky, E. F. Abou-Eladab, G. Waitz, J. Brock, and M. Tiedge Effects of N-glycan processing inhibitors on signaling events and induction of apoptosis in galectin-1-stimulated Jurkat T lymphocytes Glycobiology, December 1, 2006; 16(12): 1262 - 1271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Camby, M. Le Mercier, F. Lefranc, and R. Kiss Galectin-1: a small protein with major functions Glycobiology, November 1, 2006; 16(11): 137R - 157R. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Perone, S. Bertera, Z. S. Tawadrous, W. J. Shufesky, J. D. Piganelli, L. G. Baum, M. Trucco, and A. E. Morelli Dendritic Cells Expressing Transgenic Galectin-1 Delay Onset of Autoimmune Diabetes in Mice J. Immunol., October 15, 2006; 177(8): 5278 - 5289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Hernandez, J. T. Nguyen, J. He, W. Wang, B. Ardman, J. M. Green, M. Fukuda, and L. G. Baum Galectin-1 Binds Different CD43 Glycoforms to Cluster CD43 and Regulate T Cell Death J. Immunol., October 15, 2006; 177(8): 5328 - 5336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Perone, A. T. Larregina, W. J. Shufesky, G. D. Papworth, M. L. G. Sullivan, A. F. Zahorchak, D. B. Stolz, L. G. Baum, S. C. Watkins, A. W. Thomson, et al. Transgenic galectin-1 induces maturation of dendritic cells that elicit contrasting responses in naive and activated T cells. J. Immunol., June 15, 2006; 176(12): 7207 - 7220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Toscano, A. G. Commodaro, J. M. Ilarregui, G. A. Bianco, A. Liberman, H. M. Serra, J. Hirabayashi, L. V. Rizzo, and G. A. Rabinovich Galectin-1 Suppresses Autoimmune Retinal Disease by Promoting Concomitant Th2- and T Regulatory-Mediated Anti-Inflammatory Responses J. Immunol., May 15, 2006; 176(10): 6323 - 6332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Romero, J. C. Muino, G. A. Bianco, M. Ferrero, C. P. Juarez, J. D. Luna, and G. A. Rabinovich Circulating Anti-galectin-1 Antibodies Are Associated with the Severity of Ocular Disease in Autoimmune and Infectious Uveitis. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1550 - 1556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Stillman, D. K. Hsu, M. Pang, C. F. Brewer, P. Johnson, F.-T. Liu, and L. G. Baum Galectin-3 and Galectin-1 Bind Distinct Cell Surface Glycoprotein Receptors to Induce T Cell Death J. Immunol., January 15, 2006; 176(2): 778 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q.-T. Le, G. Shi, H. Cao, D. W. Nelson, Y. Wang, E. Y. Chen, S. Zhao, C. Kong, D. Richardson, K. J. O'Byrne, et al. Galectin-1: A Link Between Tumor Hypoxia and Tumor Immune Privilege J. Clin. Oncol., December 10, 2005; 23(35): 8932 - 8941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J M Ilarregui, G A Bianco, M A Toscano, and G A Rabinovich The coming of age of galectins as immunomodulatory agents: impact of these carbohydrate binding proteins in T cell physiology and chronic inflammatory disorders Ann Rheum Dis, November 1, 2005; 64(suppl_4): iv96 - iv103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Matarrese, A. Tinari, E. Mormone, G. A. Bianco, M. A. Toscano, B. Ascione, G. A. Rabinovich, and W. Malorni Galectin-1 Sensitizes Resting Human T Lymphocytes to Fas (CD95)-mediated Cell Death via Mitochondrial Hyperpolarization, Budding, and Fission J. Biol. Chem., February 25, 2005; 280(8): 6969 - 6985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Amano, M. Galvan, J. He, and L. G. Baum The ST6Gal I Sialyltransferase Selectively Modifies N-Glycans on CD45 to Negatively Regulate Galectin-1-induced CD45 Clustering, Phosphatase Modulation, and T Cell Death J. Biol. Chem., February 21, 2003; 278(9): 7469 - 7475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Correa, C. E. Sotomayor, M. P. Aoki, C. A. Maldonado, and G. A. Rabinovich Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory, and activated macrophages Glycobiology, February 1, 2003; 13(2): 119 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Hernandez and L. G. Baum Ah, sweet mystery of death! Galectins and control of cell fate Glycobiology, October 1, 2002; 12(10): 127R - 136R. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Rabinovich, N. Rubinstein, and L. Fainboim Unlocking the secrets of galectins: a challenge at the frontier of glyco-immunology J. Leukoc. Biol., May 1, 2002; 71(5): 741 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Dunphy, G. J. Barcham, R. J. Bischof, A. R. Young, A. Nash, and E. N. T. Meeusen Isolation and Characterization of a Novel Eosinophil-specific Galectin Released into the Lungs in Response to Allergen Challenge J. Biol. Chem., April 19, 2002; 277(17): 14916 - 14924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Nguyen, D. P. Evans, M. Galvan, K. E. Pace, D. Leitenberg, T. N. Bui, and L. G. Baum CD45 Modulates Galectin-1-Induced T Cell Death: Regulation by Expression of Core 2 O-Glycans J. Immunol., November 15, 2001; 167(10): 5697 - 5707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Zuniga, A. Gruppi, J. Hirabayashi, K. I. Kasai, and G. A. Rabinovich Regulated Expression and Effect of Galectin-1 on Trypanosoma cruzi-Infected Macrophages: Modulation of Microbicidal Activity and Survival Infect. Immun., November 1, 2001; 69(11): 6804 - 6812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dykstra, A. Cherukuri, and S. K. Pierce Rafts and synapses in the spatial organization of immune cell signaling receptors J. Leukoc. Biol., November 1, 2001; 70(5): 699 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Zuniga, G. A. Rabinovich, M. M. Iglesias, and A. Gruppi Regulated expression of galectin-1 during B-cell activation and implications for T-cell apoptosis J. Leukoc. Biol., July 1, 2001; 70(1): 73 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hotta, T. Funahashi, Y. Matsukawa, M. Takahashi, H. Nishizawa, K. Kishida, M. Matsuda, H. Kuriyama, S. Kihara, T. Nakamura, et al. Galectin-12, an Adipose-expressed Galectin-like Molecule Possessing Apoptosis-inducing Activity J. Biol. Chem., August 31, 2001; 276(36): 34089 - 34097. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
