B and T lymphocyte attenuator (BTLA) was identified as another negative checkpoint regulator in the IgSF structurally related to CTLA-4 and PD-1.


An Overview of B and T Lymphocyte Attenuator (BTLA)

B and T lymphocyte attenuator (BTLA) was identified as a negative checkpoint regulator in the IgSF. BTLA is the third inhibitory molecule found in CD28 family, mainly expressed on the surface of B & T cells, macrophages and other cells. BTLA produces inhibitory signals, which can lead to autoimmune disease and immune tolerance. The known inhibitory cosine excitons include cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed death-1 (PD-1), T cell immunoglobulin and mucin domain 3 (Tim-3), et al. BTLA has a similar structure to that of the CTLA-4, PD-1, but their expression is different. CTLA-4 and PD-1 were not expressed on resting T cells, but increased gradually after activation, while BTLA was constitutively expressed on resting T cells and continued to express after activation. BTLA signal could inhibit the proliferation of CD3 activated T cells and CHO cells which secreted the ligand HVEM and could bind to BTLA on the surface of T cells and decrease the proliferation of T cells.

Inhibition of BTLA

It was found that the combination of high immunogenicity vaccine expressing E7 and HSV-1 glycoprotein d could block the signal transduction of BTLA-HVEM and result in strong immune activity of CD8 T cells. In addition, the combination of soluble BTLA (sBTLA) and heat shock protein 70 (HSP70) also inhibited the expression of BTLA and enhanced the immune response. sBTLA could compete with BTLA in HVEM. The HSP70 vaccine could enhance Th1 cell function and promote the secretion of cytokines IL-2 and IFN-γ.

Autophagy and BTLA

The immune response of the organism is regulated by the activation and suppression signals. BTLA and its activated signal pathway mainly exert immunosuppressive effect in cellular and humoral immunity, induce immune tolerance, and is closely related to the occurrence and development of autoimmune diseases such as rheumatoid arthritis, AIDS and other infectious diseases, as well as tumor and graft versus host disease, etc. The regulation of BTLA signaling pathway is expected to be used for immunotherapy of related diseases.


Cheng Xiaoxing, Jiang Jing. A. (2012). The role of BTLA signaling pathway in immune regulation. Modern immunology. 32(3);257-260

Wang Yueying, Zhang Shijie et al. A. (2010). Regulatory role of BTLA signal in the initiation and early phase of T cell activation. Chinese Journal of Immunology. 26(4);304-308