Page 400 - Veterinary Immunology, 10th Edition

VetBooks.ir Co-Stimulators

The binding of a T cell antigen receptor to an antigen-MHC
complex is not sufficient by itself to trigger a helper T cell response.

Additional signals are needed for the T cell to respond fully. For
example, adhesion molecules must bind the T cells and antigen-
presenting cells firmly together and permit prolonged, strong
signaling between the cells. TCR-antigen binding then triggers the
initial signaling steps. Receptor molecules such as CD40 on antigen-

presenting cells bind to their ligands on T cells and amplify these
signals. T cells must also be stimulated by cytokines secreted by the
antigen-presenting cells. The cytokines determine the way in which

a T cell responds to antigen, turning on some pathways and turning
off others.

Co-Stimulatory Receptors

Several additional cellular receptors must be stimulated in order to

fully activate T cells and determine how they will respond. This is
called co-stimulation.

CD40-CD154 Signaling

CD40 is a receptor expressed on antigen-presenting cells. Its ligand
is CD154, expressed on helper T cells (Fig. 14.7). When CD154 and

CD40 bind, signals are sent in both directions. The signal from the
antigen-presenting cell to the T cell causes it to express a receptor
called CD28. The signal from the T cell to the antigen-presenting

cell stimulates it to express either CD80 or CD86. CD40-CD154
signaling also stimulates the antigen-presenting cell to secrete
multiple cytokines, including interleukin-1 (IL-1), IL-6, IL-8, IL-12,
CCL3, and tumor necrosis factor-α (TNF-α).

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