CD40 (protein)
From Wikipedia, the free encyclopedia
CD40 is a costimulatory protein found on antigen presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.[1]
[edit] Specific effects on cells
In the macrophage, the primary signal for activation is IFN-γ from Th1 type CD4 T cells. The secondary signal is CD40L on the T cell which binds CD40 on the macrophage cell surface. As a result, the macrophage expresses more CD40 and TNF receptors on its surface which helps increase the level of activation. The activated macrophage can then destroy phagocytosed bacteria and produce more cytokines.
The B cell can present antigens to helper T cells. If the T cell recognizes the peptide presented by the B cell, the T cell synthesizes CD40L. The CD40L binds to the B cell's CD40 receptor which causes resting B cell activation. The T cell also produces IL-4 which directly binds to B cell receptors. As a result of this interaction, the B cell can undergo division, antibody isotype switching, and differentiation to plasma cells. The end result is a B cell which is able to mass produce specific antibodies against an antigenic target.
[edit] References
[edit] Further reading
- Parham, Peter (2004). The Immune System, 2nd Ed, Garland Science, 169-173. ISBN 0-8153-4093-1.
- Coico R, Sunshine G, and Benjamin E (2003). Immunology: A Short Course, 97.
- Clark EA (1991). "CD40: a cytokine receptor in search of a ligand.". Tissue Antigens 36 (1): 33–6. PMID 1701063.
- Banchereau J, Bazan F, Blanchard D, et al. (1994). "The CD40 antigen and its ligand.". Annu. Rev. Immunol. 12: 881–922. doi: . PMID 7516669.
- van Kooten C, Banchereau J (2000). "CD40-CD40 ligand.". J. Leukoc. Biol. 67 (1): 2–17. PMID 10647992.
- Schattner EJ (2003). "CD40 ligand in CLL pathogenesis and therapy.". Leuk. Lymphoma 37 (5-6): 461–72. PMID 11042507.
- Bhushan A, Covey LR (2002). "CD40:CD40L interactions in X-linked and non-X-linked hyper-IgM syndromes.". Immunol. Res. 24 (3): 311–24. PMID 11817328.
- Cheng G, Schoenberger SP (2002). "CD40 signaling and autoimmunity.". Curr. Dir. Autoimmun. 5: 51–61. PMID 11826760.
- Dallman C, Johnson PW, Packham G (2003). "Differential regulation of cell survival by CD40.". Apoptosis 8 (1): 45–53. PMID 12510151.
- O'Sullivan B, Thomas R (2004). "Recent advances on the role of CD40 and dendritic cells in immunity and tolerance.". Curr. Opin. Hematol. 10 (4): 272–8. PMID 12799532.
- Benveniste EN, Nguyen VT, Wesemann DR (2004). "Molecular regulation of CD40 gene expression in macrophages and microglia.". Brain Behav. Immun. 18 (1): 7–12. PMID 14651941.
- Xu Y, Song G (2005). "The role of CD40-CD154 interaction in cell immunoregulation.". J. Biomed. Sci. 11 (4): 426–38. doi: . PMID 15153777.
- Contin C, Couzi L, Moreau JF, et al. (2004). "[Immune dysfuntion of uremic patients: potential role for the soluble form of CD40]". Néphrologie 25 (4): 119–26. PMID 15291139.
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