SLAMF6 compartmentalization enhances T cell functions
© 2022 Gartshteyn et al..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Life science alliance - 6(2023), 2 vom: 20. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gartshteyn, Yevgeniya [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.01.2023 Date Revised 09.04.2024 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.26508/lsa.202201533 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2022 Gartshteyn et al. | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Bukhari, Shoiab |e verfasserin |4 aut | |
| 700 | 1 | |a Dragovich, Matthew |e verfasserin |4 aut | |
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| 700 | 1 | |a Mor, Adam |e verfasserin |4 aut | |
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