Recombinant Human CD40 ligand (CD40LG) (C194W), partial (Active)

Function

Acts as a ligand for integrins, specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40 receptor are required for activation of CD40-CD40LG signaling, which have cell-type dependent effects, such as B-cell activation, NF-kappa-B signaling and anti-apoptotic signaling

Subcellular Location

Secreted

Disease Association

Immunodeficiency with hyper-IgM, type 1 (HIGM1) : Immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Specifically expressed on activated CD4+ T-lymphocytes

Subunit

Homotrimer (PubMed:11676606, PubMed:8589998, PubMed:8626375). Interacts with isoform 3 of CD28 (PubMed:15067037). CD40 ligand, soluble form: Exists as either a monomer or a homotrimer (PubMed:31331973, PubMed:8626375). Forms a ternary complex between CD40 and integrins for CD40-CD40LG signaling (PubMed:31331973)

• Graf D. et al. Cloning of TRAP, a ligand for CD40 on human T cells. — Eur. J. Immunol. (1992)
• Hollenbaugh D. et al. The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity. — EMBO J. (1992)
• Aruffo A. et al. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. — Cell (1993)
• Spriggs M.K. et al. Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion. — J. Exp. Med. (1992)
• Gauchat J.-F. et al. Human CD40-ligand: molecular cloning, cellular distribution and regulation of expression by factors controlling IgE production. — FEBS Lett. (1993)
• Shimadzu M. et al. Structural organization of the gene for CD40 ligand: molecular analysis for diagnosis of X-linked hyper-IgM syndrome. — Biochim. Biophys. Acta (1995)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Pietravalle F. et al. Human native soluble CD40L is a biologically active trimer, processed inside microsomes. — J. Biol. Chem. (1996)