Focal localization of placental protein 14 toward sites of TCR engagement.

Abstract

TCR signal transduction is amplified by the dynamic accumulation of accessory molecules at APC-T cell contact sites, along with the simultaneous exclusion from these sites of negative regulators, such as certain tyrosine phosphatases and large glycosylated proteins. However, given the general nature of the cytoskeleton-driven clustering mechanism underlying molecular segregation events at the APC-T cell interaction site, the possibility exists that negative regulators might similarly be segregated at these sites. Using fluorescence microscopy, we have demonstrated that placental protein 14 (PP14), a direct T cell inhibitor, focuses toward APC-T cell contact sites in conjunction with conjugate formation. We have further established that the function of PP14 is dependent upon its localization to the sites of TCR triggering, where it negatively regulates T cell activation. Thus, PP14 provides an example of a soluble negative T cell regulator whose inhibitory activity is linked to modulation of the APC-T cell contact site, thereby hindering early events triggered by the TCR.