BTLA expression is induced during activation of T cells, and BTLA remains expressed on Th1 cells but not Th2 cells. Like PD1 and CTLA4, BTLA interacts with a B7 homolog, B7H4.[2] However, unlike PD-1 and CTLA-4, BTLA displays T-Cell inhibition via interaction with tumor necrosis family receptors (TNF-R), not just the B7 family of cell surface receptors. BTLA is a ligand for tumour necrosis factor (receptor) superfamily, member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM). BTLA-HVEM complexes negatively regulate T-cell immune responses.
Clinical significance
BTLA activation inhibits the function of human CD8+ cancer-specific T cells.[3]
References
↑Watanabe N, Gavrieli M, Sedy JR, Yang J, Fallarino F, Loftin SK, Hurchla MA, Zimmerman N, Sim J, Zang X, Murphy TL, Russell JH, Allison JP, Murphy KM (Jun 2003). "BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1". Nat Immunol. 4 (7): 670–9. doi:10.1038/ni944. PMID12796776.
Pao LI, Bedzyk WD, Persin C, Cambier JC (1997). "Molecular targets of CD45 in B cell antigen receptor signal transduction". J. Immunol. 158 (3): 1116–24. PMID9013950.
Pao LI, Cambier JC (1997). "Syk, but not Lyn, recruitment to B cell antigen receptor and activation following stimulation of CD45- B cells". J. Immunol. 158 (6): 2663–9. PMID9058799.
Vilen BJ, Famiglietti SJ, Carbone AM, et al. (1997). "B cell antigen receptor desensitization: disruption of receptor coupling to tyrosine kinase activation". J. Immunol. 159 (1): 231–43. PMID9200459.
Gavrieli M, Watanabe N, Loftin SK, et al. (2004). "Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B and T lymphocyte attenuator required for association with protein tyrosine phosphatases SHP-1 and SHP-2". Biochem. Biophys. Res. Commun. 312 (4): 1236–43. doi:10.1016/j.bbrc.2003.11.070. PMID14652006.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Sedy JR, Gavrieli M, Potter KG, et al. (2005). "B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator". Nat. Immunol. 6 (1): 90–8. doi:10.1038/ni1144. PMID15568026.
Compaan DM, Gonzalez LC, Tom I, et al. (2006). "Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex". J. Biol. Chem. 280 (47): 39553–61. doi:10.1074/jbc.M507629200. PMID16169851.
Otsuki N, Kamimura Y, Hashiguchi M, Azuma M (2006). "Expression and function of the B and T lymphocyte attenuator (BTLA/CD272) on human T cells". Biochem. Biophys. Res. Commun. 344 (4): 1121–7. doi:10.1016/j.bbrc.2006.03.242. PMID16643847.
Wang XF, Chen YJ, Wang Q, et al. (2007). "Distinct expression and inhibitory function of B and T lymphocyte attenuator on human T cells". Tissue Antigens. 69 (2): 145–53. doi:10.1111/j.1399-0039.2006.00710.x. PMID17257317.