A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator.
Immune cell cosignaling receptors are important modulators of immune cell function. For T cells, cosignaling receptors supply necessary secondary signals supporting activation or attenuation after engagement of antigen-presenting cells. The primary cosignaling receptors belong to either the Ig (CD28-like) or TNF receptor ( TNFR) superfamilies. The CD28 family is comprised of coinhibitory and costimulatory receptors. The three coinhibitory receptors are cytotoxic T lymphocyte antigen 4, programmed death-1, and B and T lymphocyte attenuator (BTLA). Although cytotoxic T lymphocyte antigen 4 and programmed death-1 interact with B7-Ig family counter receptors, the ligand for BTLA is less clear. From a protein-protein interaction screen, we identified the TNFR family member herpesvirus entry mediator (HVEM) as a counter receptor for BTLA. Here we show that HVEM binds BTLA with high affinity and can form a ternary complex with its known ligands homologous to lymphotoxin, showing inducible expression, and competing with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT) or lymphotoxin alpha and BTLA. In addition, binding of HVEM to BTLA attenuates T cell activation, identifying HVEM/BTLA as a coinhibitory receptor pair. This study is a demonstration of a direct interaction between the primary T cell cosignaling receptors of the CD28 and TNFR families.[1]References
- A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator. Gonzalez, L.C., Loyet, K.M., Calemine-Fenaux, J., Chauhan, V., Wranik, B., Ouyang, W., Eaton, D.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
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