Cd40 Protein

The CD40 receptor is a 48-kDa transmembrane protein present on B cells and APCs such as dendritic cells, follicular dendritic cells, macrophages, and hematopoietic cells. Receptor signaling is initiated by binding of CD40 to its ligand (CD40L) present on activated CD4 cells (Fig. 3). Like other members of the tumor necrosis factor (TNF) superfamily, CD40L is a homotrimer shaped like a truncated pyramid. Each CD40L binds three CD40 molecules creating multimers of CD40 on the cell surface. Multimer formation is the critical step in the initiation of intracellular signaling. CD40L signaling activates a number of different cellular pathways that upregulate the expression of the B7 costimulatory molecules. Signaling also upregulates the bcl protein family (Kehry, 1996). Gene products are important in the rescue ofB cells from apoptosis (Fig. 4).

Figure 3. The role of CD40-CD40L in T-cell activation. This is a two-step model of T-cell activation, (a) Antigen-primed dendritic cells (Langerhans cells in tissue) migrate to the lymph node where they present processed antigen to T cells in the form of MHC-peptide complexes which deliver the antigenic signal. As a result, T cells upregulate CD40L on their surface, (b) The T-cell CD40L induces costimulatory activity on the dendritic cells via the CD40-CD40L interaction. Dendritic cells expressing costimulatory signals send a second costimulatory signal to T cells along with signal 1 for full activation of T cells to produce cytokines. Reprinted from Immunology Today, Grenwal and Flavell, 1996, 17:410-3, with permission of Elsevier Science.

Figure 3. The role of CD40-CD40L in T-cell activation. This is a two-step model of T-cell activation, (a) Antigen-primed dendritic cells (Langerhans cells in tissue) migrate to the lymph node where they present processed antigen to T cells in the form of MHC-peptide complexes which deliver the antigenic signal. As a result, T cells upregulate CD40L on their surface, (b) The T-cell CD40L induces costimulatory activity on the dendritic cells via the CD40-CD40L interaction. Dendritic cells expressing costimulatory signals send a second costimulatory signal to T cells along with signal 1 for full activation of T cells to produce cytokines. Reprinted from Immunology Today, Grenwal and Flavell, 1996, 17:410-3, with permission of Elsevier Science.

Figure 4. Modeling of CD40 signaling in B cells. Shaded areas of CD40 indicate the four extracellular cysteine-rich domains; cross-hatched areas of TRAF indicate TRAF-N and TRAF-C homology. Zn indicates the zinc ring finger and zinc finger domains in TRAF1, TRAF2 and TRAF3. TRAF3 is also known as CRAF1, CD40bp, or LAP1. Reprinted from The Journal of Immunology, Kehry, 1996, 156:2345-8. Copyright 1996, The American Association of Immunologists.

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