|
|
|
|
|
|
|
||
Brief Definitive Report |
Address correspondence to Anne I. Sperling, Dept. of Medicine, Section of Pulmonary and Critical Care Medicine, MC6026, M624, 5841 S. Maryland Ave. Chicago, IL 60637. Phone: (773) 834-1211; Fax: (773) 702-4736; email: asperlin{at}uchicago.edu
CD43 is a large heavily glycosylated protein highly expressed on T cells and actively excluded from the immunological synapse through interactions with ezrin-radixin-moesin proteins. Due to its size and charge, it has been proposed that the CD43 ectodomain acts as a physical barrier to T cell–APC interactions. We have addressed this hypothesis by studying the effect of reconstituting CD43 mutants into the hyperproliferative CD43–/– T cells. Reintroduction of full-length CD43 reversed the CD43–/– T cell hyperproliferation. Interestingly, despite the lack of exclusion from the interaction site, a mutant containing the CD43 ectodomain on a glycosylphosphatidylinositol linkage was ineffective. Additionally, T cell–APC conjugate formation was not affected by this ectodomain-only construct. In contrast, CD43–/– T cell hyperproliferation was reversed by an intracellular-only CD43 fused to the small ectodomain of hCD16. Mutation of this intracellular-only CD43 such that it could not move from the T cell–APC contact site had no further affect on proliferation than the moveable CD43 but did dramatically reduce interleukin-2 production. Thus, the exclusion of the CD43 intracellular region from the immunological synapse is required for CD43 regulation of interleukin-2 production, but the presence of the cytoplasmic tail, independent of its location, is sufficient to reverse CD43–/– T cell hyperproliferation.
Key Words: CD43 • CD25 • proliferation • adhesion • SMAC
The online version of this article contains supplemental material.
Abbreviations used in this paper: DO.CD43–/–, DO.11.10.CD43–/–; CD16-7, the ectodomain of human CD16 fused to the transmembrane of human CD7; CD16-7-43, the CD16-7 construct fused to the ICD of murine CD43; CD16-7–NGG, CD16-7-43 with the ERM binding KRR motif mutated to the ERM nonbinding NGG motif; CD43FL, full-length murine CD43; CD43GPI, the ectodomain of murine CD43 fused to a GPI anchor; CD43–NGG, the full-length mCD43 with the ERM binding KRR motif mutated to the ERM non-binding NGG motif; CFSE, carboxyfluorescein diacetate succinimidyl ester 5-(and 6-); C-SMAC, central supramolecular activation cluster; ECD, extracellular domain; ERM, ezrin-radixin-moesin; GPI, glycosylphosphatidylinositol; ICD, intracellular domain.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
