CD40 is a type I membrane protein whose extracellular domain contains four cysteine-rich domains which are the hallmark of the TNF receptor superfamily. CD40 was first identified through an antibody, G28-5, which induces B cell proliferation, but only in the presence of an anti-mu or an anti-CD20 antibody.
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|Synonym:||Bp50, CDW40, MGC9013, p50, TNFRSF5|
|Tag:||None (The affinity tag, Mouse IgG2a Fc, has been removed by TEV protease).|
|Construction:||Human CD40 (E21-R193)-TEV protease cleavage site-mouse IgG2a Fc|
|MW (calculated):||20,599 daltons|
|MW (SDS-PAGE):||22 Kd|
|Abs 0.1% (= 1 mg/ml):||1.079|
CD40 is a type I membrane protein whose extracellular domain contains four cysteine-rich domains which are the hallmark of the TNF receptor superfamily. CD40 was first identified through an antibody, G28-5, which induces B cell proliferation, but only in the presence of an anti-mu or an anti-CD20 antibody. CD40, initially identified on the surface of B cells as Bp50 and was cloned via expression cloning.
CD40 ligation was shown to activate CD18/11a-mediated adhesion to increase IL-6 expression, and together with IL-4 to induce isotype class switching to IgE. The important findings that CD40 ligation is critical for preventing B cells from dying, it plays a role in germinal center formation and how lymphocytes are protected from apoptosis were made prior to the discovery of CD40L and connecting CD40 as a mediator for T cell’s helper functions. However, the discovery of the CD40L firmly established the CD40-CD40L interaction as an indispensable axis in the T-cell-dependent B-cell responses. In addition to its regulatory function in humoral immunity, CD40 is an attractive oncological target as it is expressed on lymphoid malignancies and on a range of carcinomas. Ligation of CD40 on some cancer cells can lead to cell death. Hence, anti-CD40 antibodies may follow the footstep of anti-CD20 antibodies, such as Rituximab, as treatment for a variety of lymphomas.
Soluble CD40 has been demonstrated to be an effective decoy for inhibiting the functional activity of CD40L.
Amino Acid Sequence.
1. Clark EA, Ledbetter JA. (1986) Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A. 83:4494-4498
2. Stamenkovic I, Clark EA, Seed B. (1989) A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J. 8:1403-1410
3. Hassan SB, Sørensen JF, Olsen BN, Pedersen AE. (2014) Anti-CD40-mediated cancer immunotherapy: an update of recent and ongoing clinical trials. Immunopharmacol Immunotoxicol. 36:96-104.