Submitted January 4, 2007
Accepted June 19, 2007
Signaling through CD43 regulates CD4 T cell trafficking
Purvi D Mody, Judy L Cannon, Hozefa S Bandukwala, Kelly M Blaine, Alexander B Schilling, Kevin Swier, and Anne I Sperling*
Committee on Immunology, University of Chicago, Chicago, IL, United States
Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, United States
Proteomics and Informatics Services Facility, University of Illinois at Chicago, Chicago, IL, United States
Department of Biological Sciences, Chicago State University, Chicago, IL, United States
* Corresponding author; email: asperlin{at}uchicago.edu.
The mucin-like protein CD43 is excluded from the immune synapse, and regulates T cell proliferation as well as T cell migration. While the CD43 cytoplasmic domain is necessary for regulation of T cell activation and proliferation, the mechanism via which CD43 regulates trafficking is not well defined. To investigate whether CD43 phosphorylation regulates its function in T cells, we used tandem mass spectrometry and identified Ser76 in murine CD43 as a previously unidentified site of basal phosphorylation. Interestingly, mutation of this single serine to alanine greatly diminishes T cell trafficking to the lymph node, while CD43 exclusion and CD43-mediated regulation of T cell proliferation remain intact. Further, the CD43 extracellular domain was also required for T cell trafficking, providing a hitherto unknown function for the extracellular domain, and suggesting that the extracellular domain may be required to transduce signals via the cytoplasmic domain. These data reveal a novel mechanism by which CD43 regulates T cell function, and suggest that CD43 functions as a signaling molecule, sensing extracellular cues, and transducing intracellular signals that modulate T cell function.
