| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CUTTING EDGE |
* Department of Biology and
Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223;
Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003;
Department of Internal Medicine, Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06520; and
¶ Department of Internal Medicine, Section of Immunobiology, University of Vermont, Burlington, VT 05405
Salp15 is an Ixodes scapularis salivary protein that inhibits CD4+ T cell activation through the repression of TCR ligation-triggered calcium fluxes and IL-2 production. We show in this study that Salp15 binds specifically to the CD4 coreceptor on mammalian host T cells. Salp15 specifically associates through its C-terminal residues with the outermost two extracellular domains of CD4. Upon binding to CD4, Salp15 inhibits the subsequent TCR ligation-induced T cell signaling at the earliest steps including tyrosine phosphorylation of the Src kinase Lck, downstream effector proteins, and lipid raft reorganization. These results provide a molecular basis to understanding the immunosuppressive activity of Salp15 and its specificity for CD4+ T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the National Institutes of Health (to V.T., E.F., M.R., and J.A.) and American Health Association (to N.R. and C.M.Y.). E.F. is the recipient of a Burroughs Wellcome clinical scientist award in translational research. J.K.K. is the recipient of a University of North Carolina at Charlotte faculty research award.
2 R.G. and I.J.J. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Juan Anguita, Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 103 Paige Lab 161 Holdsworth Way, Amherst, MA 01003. E-mail address: janguita{at}vasci.umass.edu
4 Abbreviations used in this paper: PLC, phospholipase C; TR, thioredoxin; sCD4, soluble CD4; CTB, cholera-toxin B.
This article has been cited by other articles:
|
|
 |
|
  A. Skallova, G. Iezzi, F. Ampenberger, M. Kopf, and J. Kopecky Tick Saliva Inhibits Dendritic Cell Migration, Maturation, and Function while Promoting Development of Th2 Responses J. Immunol., May 1, 2008; 180(9): 6186 - 6192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Ashish, I. J. Juncadella, R. Garg, C. D. Boone, J. Anguita, and J. K. Krueger Conformational Rearrangement within the Soluble Domains of the CD4 Receptor Is Ligand-specific J. Biol. Chem., February 1, 2008; 283(5): 2761 - 2772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vojdani, F. Hebroni, Y. Raphael, J. Erde, and B. Raxlen Novel Diagnosis of Lyme Disease: Potential for CAM Intervention Evid. Based Complement. Altern. Med., October 15, 2007; (2007) nem138v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Paveglio, J. Allard, J. Mayette, L. A. Whittaker, I. Juncadella, J. Anguita, and M. E. Poynter The Tick Salivary Protein, Salp15, Inhibits the Development of Experimental Asthma J. Immunol., June 1, 2007; 178(11): 7064 - 7071. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
