Association of MHC class II–peptide complexes with plasma membrane lipid microdomains

Activation of CD4+ T cells requires the interaction of multiple T-cell receptors with MHC class II–peptide complexes on the surface of antigen-presenting cells (APCs). Recent studies have shown that MHC class II complexes are clustered in APC plasma membrane microdomains, thereby providing a mechanism for localized concentration of MHC class II–peptide complexes. The integrity of one type of APC membrane microdomain, the lipid raft, is important for antigen presentation to T cells. We propose a model in which the coordinated processes of MHC class II peptide loading and intracellular trafficking enhance T-cell activation by loading specific MHC class II–peptide complexes in discrete lipid raft microdomains.