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PMID:15117976
| Citation |
Tong, J, Allenspach, EJ, Takahashi, SM, Mody, PD, Park, C, Burkhardt, JK and Sperling, AI (2004) CD43 regulation of T cell activation is not through steric inhibition of T cell-APC interactions but through an intracellular mechanism. J. Exp. Med. 199:1277-83 |
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| Abstract |
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. |
| Links |
PubMed PMC2211903 Online version:10.1084/jem.20021602 |
| Keywords |
Animals; Antigen-Presenting Cells/immunology; Antigens, CD/genetics; Antigens, CD/immunology; Antigens, CD43; Cell Communication/immunology; Fluorescent Antibody Technique; Interleukin-2/biosynthesis; Interleukin-2/genetics; Lymphocyte Activation; Mice; Mice, Knockout; Sialoglycoproteins/deficiency; Sialoglycoproteins/genetics; Sialoglycoproteins/immunology; T-Lymphocytes/immunology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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