SLAMF6 clustering is required to augment T cell activation

• DOI: 10.1371/journal.pone.0218109
• Publication Date: 2019-06-14T17:37:48Z
• Authors: Matthew A. Dragovich; Kieran Adam; Marianne Strazza; Anna S. Tocheva; Michael Peled; Adam Mor
• Keywords: Ectodomain; Immunological synapse; Jurkat cells

The signaling lymphocytic activation molecule (SLAM) family is comprised of nine distinct receptors that are expressed exclusively on hematopoietic cells. Most these transmembrane homotypic by nature and downstream occurs when cells express the same SLAM receptor interact. Previous studies have determined anti-SLAMF6 antibodies can a therapeutic effect in autoimmunity cancer. However, little known about role SLAMF6 adaptive immune responses order to utilize interventional approaches, better understanding biology this T cell warranted. Accordingly, objective our study was investigate both functionally structurally (TCR) mediated responses. Biochemical genetic experiments revealed required for productive TCR signaling. Interestingly, ectodomain its function, but not recruitment immunological synapse. Flow-cytometry analysis demonstrated tyrosine 308 tail crucial ability enhance function. Imaging clustering, specifically with TCR, resulted dramatic increase Mechanistically, we showed enhanced function increasing adhesiveness through small GTPase Rap1. Taken together an important regulator where endodomain contribute differentially functions. Additional underway evaluate approaches specific human diseases.