TY - JOUR T1 - SLAMF6 compartmentalization enhances T cell functions JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201533 VL - 6 IS - 2 SP - e202201533 AU - Yevgeniya Gartshteyn AU - Anca D Askanase AU - Ruijiang Song AU - Shoiab Bukhari AU - Matthew Dragovich AU - Kieran Adam AU - Adam Mor Y1 - 2023/02/01 UR - https://www.life-science-alliance.org/content/6/2/e202201533.abstract N2 - Signaling lymphocyte activation molecule family member 6 (SLAMF6) is a T cell co-receptor. Previously, we showed that SLAMF6 clustering was required for T cell activation. To better understand the relationship between SLAMF6 location and function and to evaluate the role of SLAMF6 as a therapeutic target, we investigated how its compartmentalization on the cell surface affects T cell functions. We used biochemical and co-culture assays to show that T cell activity is enhanced when SLAMF6 colocalizes with the CD3 complex. Mechanistically, co-immunoprecipitation analysis revealed the SLAMF6-interacting proteins to be those essential for signaling downstream of T cell receptor, suggesting the two receptors share downstream signaling pathways. Bispecific anti-CD3/SLAMF6 antibodies, designed to promote SLAMF6 clustering with CD3, enhanced T cell activation. Meanwhile, anti-CD45/SLAMF6 antibodies inhibited SLAMF6 clustering with T cell receptor, likely because of the steric hindrance, but nevertheless enhanced T cell activation. We conclude that SLAMF6 bispecific antibodies have a role in modulating T cell responses, and future work will evaluate the therapeutic potential in tumor models. ER -