The Journal of Experimental Medicine
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Published online 26 April 2004 doi:10.1084/jem.20021602
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 9, 1277-1283
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Brief Definitive Report

 CD43 Regulation of T Cell Activation Is Not through Steric Inhibition of T Cell–APC Interactions but through an Intracellular Mechanism

Jiankun Tong1, Eric J. Allenspach1, Stephenie M. Takahashi1, Purvi D. Mody1, Chan Park1, Janis K. Burkhardt2, and Anne I. Sperling1

1 The Committee on Immunology and Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637
2 Department of Pathology, Children's Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, PA 19104

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

J. Tong and E.J. Allenspach contributed equally to this work.

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.


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