CD45-associated protein promotes the response of primary CD4 T cells to low-potency T-cell receptor (TCR) stimulation and facilitates CD45 association with CD3/TCR and Lck

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.