Figure 3.

Mechanisms of enhanced antigen presentation and T cell activation downstream of IgG-IG binding to low-affinity FcγRs on APCs. 1. IgG-IC mediated cross-linking of activating low-affinity FcγRs leads to src kinase mediated ITAM phosphorylation, which induces the activation of several downstream cell-type specific kinases such as lyn, syk, and eventually PI3K, resulting in increased intracellular calcium and activation of the cell. Inhibitory (ITIM) containing FcγRs such as FcγRIIB can also be expressed at the cell surface; preferentially engaging inhibitory FcγR signaling would inhibit cellular activation as described in section the molecular machinery downstream of FcγR. 2. Cellular activation triggers transcriptional programs inside the APC such as enhanced expression of pro-inflammatory cytokines (e.g., IL-6, IL-15, IL-10) as well as up-regulation of membrane-bound co-activating molecules including CD80 and CD86. 3. IgG-IC mediated FcγR crosslinking results in MHC class I and II driven presentation of antigen-derived peptides to T cells. Subsequent T cell activation via T cell receptor: MHC interaction is enhanced by concomitant co-stimulation of the T cell through CD80/CD86 engagement of CD28 as well as priming of the immune response (i.e., Th1 vs. Th17) through pro-inflammatory cytokines released by the APC in the microenvironment.