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Inhibitory TIGIT signalling is dependent on activating T cell receptor signalling

ABSTRACT: TIGIT is an immune checkpoint receptor that can signal via its intracellular inhibitory motifs to inhibit T cells, though the mechanisms remain poorly defined. To elucidate inhibitory signalling interactors of TIGIT, proximity proteomics was employed in model Jurkat T cells expressing TIGIT fused to APEX2. This identified several ligation-specific TIGIT interactors, including proteins involved in signalling (Grb2 and SOS1), cytoskeletal (CD2AP and SdcBP), and endocytic processes (IST1 and SNX3). A TIGIT mutant incapable of signalling via its inhibitory motifs prevented the recruitment of these proteins, indicating inhibitory signalling-specific engagement of these pathways. Furthermore, TIGIT engagement with these pathways, in addition to its phosphorylation and internalisation, was dependent on T cell activation as well as TIGIT ligation. Collectively, these findings demonstrate that TIGIT inhibitory signalling is restricted to activated T cells, indicating a regulatory mechanism that limits inhibition to when functionally required.

INSTRUMENT(S): Orbitrap Exploris 480, Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, T Cell, Cell Culture

SUBMITTER: William Zammit

LAB HEAD: Jonathan D. Worboys

PROVIDER: PXD063349 | Pride | 2025-05-14

REPOSITORIES: pride

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			Action	DRS
	155vs111_111_1.raw	Raw
	155vs111_111_2.raw	Raw
	155vs111_111_3.raw	Raw
	155vs111_155_1.raw	Raw
	155vs111_155_2.raw	Raw

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