Identification of proteins which interact with the cytoplasmic domain of CTLA-4

CTLA-4 is a lymphocyte cell surface receptor which has sequence homology to the T cell costimulatory receptor CD28. Unlike CD28, CTLA-4 is expressed only upon T cell activation and appears to function as a negative regulator of T cell activation. How CTLA-4 carries out this function is largely unknown. In order to better understand the signalling properties of CTLA-4, we utilized the yeast two-hybrid system to identify clones from an activated mouse T cell cDNA library that can interact with the cytoplasmic tail of CTLA-4. Out of 150 clones initially found to be positive, 17 reproducibly interacted with CTLA-4 but not with the cytoplasmic tails of CD28 or CD30. Sequencing revealed that several of these clones encode for known proteins. We are currently in the process of further characterizing the interactions between these proteins and CTLA-4, and of identifying which proteins may be potentially important for the negative regulatory function of CTLA-4.

Duke Scholars

Author Colin S Duckett Pathology