Reactome | Co-inhibition by BTLA

Co-inhibition by BTLA

Stable Identifier

R-HSA-9927353

DOI

10.3180/R-HSA-9927353.1

Type

Pathway

Species

Homo sapiens

Compartment

plasma membrane

Synonyms

BTLA inhibitory Signaling

ReviewStatus

5/5

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BTLA (B and T Lymphocyte Attenuator) is a co-inhibitory receptor that plays a crucial role in regulating immune responses, maintaining immune homeostasis, and preventing autoimmunity. BTLA interacts with its ligand, HVEM (Herpesvirus Entry Mediator), a member of the tumor necrosis factor receptor (TNFR) family. Upon engagement with HVEM, BTLA recruits the Src homology region 2 domain-containing phosphatases SHP-1 and SHP-2 to its cytoplasmic tail. These phosphatases dephosphorylate key signaling molecules downstream of the T cell receptor (TCR), effectively dampening TCR-mediated signaling and inhibiting T cell activation.
This signaling pathway is essential for modulating the immune response, particularly in maintaining peripheral tolerance and preventing the overactivation of T cells that can lead to autoimmune diseases. BTLA is expressed on various immune cells, including T cells, B cells, and dendritic cells, and it functions similarly to other immune checkpoint molecules like CTLA-4 and PD-1, but it has unique structural and functional properties.
BTLA's interaction with HVEM also influences the function of other immune cells. For instance, HVEM is expressed on many cell types, including T cells, B cells, and myeloid cells, and its interaction with BTLA can modulate the immune response in a context-dependent manner. This complex interplay is crucial for fine-tuning immune responses and ensuring that immune activation is appropriately regulated.

Literature References

PubMed ID	Title	Journal	Year
12796776	BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1 Watanabe, N, Gavrieli, M, Sedý, JR, Yang, J, Fallarino, F, Loftin, SK, Hurchla, MA, Zimmerman, N, Sim, J, Zang, X, Murphy, TL, Russell, JH, Allison, JP, Murphy, KM	Nat Immunol	2003
17145304	BTLA and HVEM cross talk regulates inhibition and costimulation Gavrieli, M, Sedy, J, Nelson, CA, Murphy, KM	Adv Immunol	2006