Project Summary Many proteins are modified after they are produced in cells. Such modification can critically influence the function of proteins. One such modification is citrullination, which has been shown to regulate the function of immune cells, including lymphocytes and neutrophils. Abnormal citrullination has been associated with many human diseases, including infection and autoimmune diseases. Thus, manipulating protein citrullination can be beneficial in many clinical settings; however, our knowledge of citrullination is still very limited mainly due to lack of sensitive and specific tool for detecting citrullination. The objectives of this project are to develop a reagent that can reliably detect the citrullination of a protein named RORgt, which is important for the differentiation/function of lymphocytes, and to demonstrate the value of this reagent in a proof-of-principle experiment. The reagent thus generated will be a powerful tool for future studies on the regulatory roles of citrullination in the function of lymphocytes and very likely will lead to discoveries of novel therapeutic targets of human diseases.