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An N-terminal tyrosine residue in the immunoreceptor tyrosine-based inhibitory motif (ITIM)-like stretch is, however, not involved in the delivery of co-inhibitory signal.
Typically, checkpoint molecules possess unique intracellular motifs to deliver inhibitory signals, such as ITIM (immunoreceptor tyrosine-based inhibitory motif), which are crucial to render T cells that undergo functionally unresponsive status.
Similar to PD-1 and CTLA-4, BTLA has one IgV domain in extracellular domain, followed by transmembrane domain and intracellular domain, where two ITIM motifs exist.
By interacting with HVEM, BTLA delivers inhibitory signal into activated T cells by recruiting SHP-1/2 via its intracellular ITIM motifs [28, 29].
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