Scaffold and Adapter Molecules in Immune Receptor Signaling

Lymphocyte activation via T and B cell receptor (TCR/BCR) ligation relies upon essential scaffold and adapter proteins for signal transduction. Scaffolds and adapters include specific polypeptide motifs and modular domains that enable protein-protein and protein-lipid interactions. Although these molecules do not harbor intrinsic enzymatic activity, scaffolds and adapters coordinate the assembly of dynamic, complex macromolecular signalosomes with carefully calibrated spatiotemporal orientation. Here we examine key adapters and scaffolds involved in two critical junction points in the proximal TCR signaling pathway: (1) activation of phospholipase C gamma 1 (PLCγ1) via the LAT-SLP76-GADS complex, and (2) activation of NF-κB via the CARD11-BCL10-MALT1 (CBM) complex. In reviewing salient findings from both mouse and human studies, this chapter highlights how scaffold/adapter components in both signalosomes are essential for T cell development, activation, differentiation and/or effector functions.