Recombinant Human CD40 Ligand/CD40L

CD40 Ligand (CD40L), also known as TNFSF, CD154, TRAP, and gp39, is a 34-39 kDa type II transmembrane glycoprotein that belongs to the TNF superfamily ^[1-3]. Mature human CD40 Ligand consists of a 22 amino acid (aa) cytoplasmic domain, a transmembrane segment, and an 215 aa extracellular region ^{[4, 5]}. The extracellular domain of human CD40 Ligand shares 74% and 76% aa sequence identity with mouse and rat CD40 Ligand, respectively. Similar to other TNF superfamily members, CD40 Ligand forms a bioactive homotrimer, both as membrane bound and soluble forms ^[6-9]. The 18 kDa soluble form (aa 113-261) arises from proteolytic processing. Mutation and alternative splicing generate additional forms of CD40 Ligand that are often truncated or non-trimerizable ^[8]. CD40 Ligand is expressed on platelets, as well as on activated T cells and B cells, basophils, eosinophils, fibroblasts, mast cells, monocytes, natural killer cells, vascular endothelial cells, and smooth muscle cells. CD40 Ligand binds to CD40, which is expressed on the surface of B cells, dendritic cells, macrophages, monocytes, platelets, endothelial, and epithelial cells (10). The interaction of CD40 Ligand with CD40 initiates signaling in both CD40 and CD40 Ligand expressing cells ^[11]. CD40 ligation by CD40 Ligand promotes B cell activation and T cell-dependent humoral responses ^{[12, 13]}. CD40 Ligand dysregulation on T cells and antigen presenting cells contributes to the immune deficiency associated with HIV infection and AIDS ^{[14, 15]}. It is also implicated in the pathology of multiple cardiovascular diseases including atherosclerosis, atherothrombosis, and restenosis ^{[16, 17]}.

Reference

[1]. Zhang, G. (2004) Curr. Opin. Struct. Biol. 14:154.

[2]. Hehlgans, T. and K. Pfeffer (2005) Immunology 115:1.

[3]. Quezada, S.A. et al. (2004) Annu. Rev. Immunol. 22:307.

[4]. Graf, D. et al. (1992) Eur. J. Immunol. 22:3191.

[5]. Hollenbaugh, D. et al. (1992) EMBO J. 11:4313.

[6]. Khandekar, S.S. et al. (2001) Protein Expr. Purif. 23:301.

[7]. Pietravalle, F. et al. (1996) J. Biol. Chem. 271:5965.

[8]. Garber, E. et al. (1999) J. Biol. Chem. 274:33545.

[9]. Vakkalanka, R.K. et al. (1999) Arthritis Rheum. 42:871.

[10]. van Kooten, C. and J. Banchereau (1997) Curr. Opin. Immunol. 9:330.

[11]. Eissner, G. et al. (2004) Cytokine Growth Factor. Rev. 15:353.

[12]. Rickert, R.C. et al. (2011) Immunol. Rev. 244:115.

[13]. Elgueta, R. et al. (2009) Immunol. Rev. 229:152.

[14]. Kornbluth, R.S. (2000) J. Leukoc. Biol. 68:373.

[15]. Chougnet, C. (2003) J. Leukoc. Biol. 74:702.

[16]. Pamukcu, B. et al. (2011) Ann. Med. 43:331.

[17]. Hassan, G.S. et al. (2012) Immunobiology 217:521