CD154(CD40L)-muCD8 Biotinylated
Human CD154 (CD40 Ligand) is a member of the tumor necrosis factor (TNF) family and is expressed on the surface of activated T cells. It can undergo proteolytic cleavage into a 19kD immunologically active soluble form. Interaction of CD154 and CD40 is essential for isotype switching in B cells. Known genetic defects that alter this interaction lead to impaired immune system function (1). Increased levels of CD154 has been associated with autoimmune disorders including SLE, CLL and eosinophilic fasciitis (5,9,10,11). CD154 has been reported to be expressed on vascular endothelial cells, smooth muscle cells, macrophages and activated platelets indicating a role for the CD40-CD154 immunoregulatory signaling in arthrosclerosis and cardiovascular disorders (7,12,13).
Molecular Structure: A soluble molecule consisting of the extracellular domain (213aa) of human CD154 fused to the extracellular domain (167aa) of murine CD8 alpha, with a predicted monomeric molecular weight of 42.6 kd. A similar construct described in reference (9).
Transfectant Cell Line: CHO
Functional Application: Human CD154-muCD8 binds to cell surface expressed human CD40 and this binding is blocked by anti-human CD154 monoclonal antibody. Recombinant CD154-muCD8 has been shown to induce phosphorylation of ERK, JNK and p38 molecules and subsequent activation of NFkB pathway (14, 15, 16) and to stimulate B cell proliferative response (19, 21). It crossreacts with CD40 in other species including pig (17)and dog(18).
References:
1)D. Gray, et al, (1994) Seminars in Immunol 6: 303-310.
2) A.C. Grammer, et al, (1995) J Immunol 154: 4996-5010.
3) F. Pietravalle, et al, (1996) J Biol Chemistry 271: 5965-5967.
4) R.J. Noelle, (1996) Immunity 4: 415-419.
5) A. Desai-Mehta, et al, (1996) J Clin Invest 97: 2063-2073.
6) I.S. Grewal and R.A. Flavell, (1996) Immunol Today 17: 410-414.
7) F. Mach, et al, (1997) Proc Natl Acad Sci USA 94:1931-1936.
8) A.C. Grammer, et al, (1999) J Immunol 163: 4150-4159.
9) D. Hollenbaugh, (1992) EMBO 11: 4314-4321.
10) R.K. Vakkalanka, et al, (1999) Arthritis Rhem 42:871-81.
11) M. Jinnin, et al.(2003) Ann Rhem Dis 62: 190-191.
12) U. Schonbeck, et al, (2000) PNAS USA 97: 7458-7463.
13) U. Schonbeck, et al, (2001) Circulation 104: 2266-2268.
14) AC Grammer, PF Lipsky, et al (2000) Advances in Immunology 76: 61-178.
15) AC Grammer, PF Lipsky, et al (2004) Arthristis Research and Therapy 6: 28-38.
16). Melter M, D M Briscoe, et al (2000) Blood 96:3801-3808.
17). Takamatsu H, RME Parkhouse, et al. (1999) Immunology 97(2):211-213.
18) Daisuke I, J F Modiano, et al. (2012) Leukemia and Lymphoma 53(7): 1390-1398
19) Brodeur SR, RS Geha, et al. (2003) Immunity 18(6): 837-848
20) KC Bankert, GA Bishop, et al.(2015) J Immunol 194(9): 4319-4327. PMID: 25795759.ID:
21) CR Smulski, S Fournel, et al. (2017) Cell Death and Disease 8(2):e2601. doi: 10.1038/cddis.2017.22. PMID: 28182009