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Murine Tim-1 is excluded from the immunological synapse

Kane, LP and Lin, J and Chen, L (2012) Murine Tim-1 is excluded from the immunological synapse. F1000Research, 1. ISSN 2046-1402

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The interaction between T cells and APCs bearing cognate antigen results in the formation of an immunological synapse (IS). During this process, many receptors and signaling proteins segregate to regions proximal to the synapse. This protein movement is thought to influence T cell function. However, some proteins are transported away from the IS, which is controlled in part by ERM family proteins. Tim-1 is a transmembrane protein with co-stimulatory functions that is found on many immune cells, including T cells. However, the expression pattern of Tim-1 on T cells upon activation by APCs has not been explored. Interestingly, in this study we demonstrate that the majority of Tim-1 on activated T cells is excluded from the IS. Tim-1 predominantly resides outside of the IS, and structure/function studies indicate that the cytoplasmic tail influences Tim-1 polarization. Specifically, a putative ERM binding motif (KRK 244-246) in the Tim-1 cytoplasmic tail appears necessary for proper Tim-1 localization. Furthermore, mutation of the KRK motif results in enhanced early tyrosine phosphorylation downstream of TCR/CD28 stimulation upon ectopic expression of Tim-1. Paradoxically however, the KRK motif is necessary for Tim-1 co-stimulation of NFAT/AP-1 activation and co-stimulation of cytokine production. This work reveals unexpected complexity underlying Tim-1 localization and suggests potentially novel mechanisms by which Tim-1 modulates T cell activity.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kane, LPlkane@pitt.eduLKANE0000-0001-5198-516X
Lin, J
Chen, Llcc23@pitt.eduLCC23
ContributionContributors NameEmailPitt UsernameORCID
Date: 10 October 2012
Date Type: Publication
Journal or Publication Title: F1000Research
Volume: 1
DOI or Unique Handle: 10.12688/f1000research.1-10.v2
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
ISSN: 2046-1402
Date Deposited: 08 Aug 2016 20:19
Last Modified: 13 Jun 2023 11:55


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