B and T lymphocyte attenuator interacts with CD3ζ and inhibits tyrosine phosphorylation of TCRζ complex during T‐cell activation

B and T lymphocyte attenuator (BTLA) is an important negative regulator of T‐cell activation. T‐cell activation involves partitioning of receptors into discrete membrane compartments known as lipid rafts and the formation of an immunological synapse (IS) between the T cell and antigen‐presenting cell (APC). Here we show that after T‐cell stimulation, BTLA co‐clusters with the CD3 ζ and is then involved in IS, as determined by a two‐photon microscope. BTLA can interact with the phosphorylated form of T‐cell receptor (TCR) within the lipid raft, which is associated with the T‐cell signaling complex. Coligation of BTLA with the TCR significantly decreased the amount of phosphorylated TCR‐related signal accumulation in the lipid raft during T‐cell activation. These results suggest that BTLA functions to regulate T‐cell signaling by controlling the phosphorylated form of TCR ζ accumulation in the lipid raft.