B and T lymphocyte attenuator interacts with CD3zeta and inhibits tyrosine phosphorylation of TCRzeta 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 CD3zeta 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 TCRzeta accumulation in the lipid raft.
Wu
Ting-He
TH
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zhen
Yu
Y
Zeng
Chun
C
Yi
Huan-Fa
HF
Zhao
Yong
Y
D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D021962:Membrane Microdomains / Q000187:drug effects; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine / Q000276:immunology*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
C488868:BTLA protein, mouse; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; C054979:antigen T cell receptor, zeta chain; D019000:Phosphotyrosine