PT  - JOURNAL ARTICLE
AU  - Gartshteyn, Yevgeniya
AU  - Askanase, Anca D
AU  - Song, Ruijiang
AU  - Bukhari, Shoiab
AU  - Dragovich, Matthew
AU  - Adam, Kieran
AU  - Mor, Adam
TI  - SLAMF6 compartmentalization enhances T cell functions
AID  - 10.26508/lsa.202201533
DP  - 2023 Feb 01
TA  - Life Science Alliance
PG  - e202201533
VI  - 6
IP  - 2
4099  - https://www.life-science-alliance.org/content/6/2/e202201533.short
4100  - https://www.life-science-alliance.org/content/6/2/e202201533.full
SO  - Life Sci. Alliance2023 Feb 01; 6
AB  - 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.