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

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 in...

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Detalles Bibliográficos
Autores principales: Tong, Jiankun, Allenspach, Eric J., Takahashi, Stephenie M., Mody, Purvi D., Park, Chan, Burkhardt, Janis K., Sperling, Anne I.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211903/
https://www.ncbi.nlm.nih.gov/pubmed/15117976
http://dx.doi.org/10.1084/jem.20021602
Descripción
Sumario: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.