Authors: Leitenberg, David; Falahati, Rustom¹; Lu, Dan Dan¹; Takeda, Akiko²

Source: Immunology, Volume 121, Number 4, August 2007 , pp. 545-554(10)

Publisher: Wiley-Blackwell

Abstract:

Summary

Although it is clear that the CD45 tyrosine phosphatase is required for efficient T-cell activation and T-cell development, the factors that regulate CD45 function remain uncertain. Previous data have indicated that there is an association of CD45 with CD4 and the T-cell receptor (TCR) complex controlled by the variable ectodomain of CD45 and, following activation, by high- and low-potency peptides. This suggests that controlling substrate access to CD45 may be an important regulatory mechanism during T-cell activation. In the present study we have examined the role of the transmembrane adapter-like molecule CD45-associated protein (CD45-AP) in regulating the association of CD45 with CD3/TCR and lck, and in regulating primary CD4⁺ T-lymphocyte activation. In CD4⁺ T cells from CD45-AP-deficient mice, coimmunoprecipitation of CD45 with the CD3/TCR complex, in addition to lck, is significantly reduced compared with wild-type T cells. Functionally, this correlates with a decreased proliferative response, a decrease in interleukin (IL)-2 production, and a decrease in calcium flux upon stimulation with a low-potency altered peptide ligand. However, the response of CD45-AP-deficient T cells to stimulation with a high-avidity agonist peptide was largely intact, except for a modest decrease in IL-2 production. These data suggest that CD45-AP promotes or stabilizes the association of CD45 with substrates and regulates the threshold of T-cell activation.

Keywords: T lymphocyte; phosphatase; kinase; CD45

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2567.2007.02602.x

Affiliations: 1: Department of Microbiology, Immunology and Tropical Medicine, George Washington University Medical Center, Washington, DC 2: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Publication date: 2007-08-01

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