MHC II and the Endocytic Pathway: Regulation by Invariant Chain

The major histocompatibility complex (MHC) class I and II molecules perform vital functions in innate and adaptive immune responses towards invading pathogens. MHC class I molecules load peptides in the endoplasmatic reticulum (ER) and display them to the T cell receptors (TcR) on CD8(+) T lymphocytes. MHC class II molecules (MHC II) acquire their peptides in endosomes and present these to the TcR on CD4+ T lymphocytes. They are vital for the generation of humoral immune responses. MHC II assembly in the ER and trafficking to endosomes is guided by a specialized MHC II chaperone termed the invariant chain (Ii). Ii self-associates into a trimer in the ER, this provides a scaffold for the assembly of three MHC II heterodimers and blocks their peptide binding grooves, thereby avoiding premature peptide binding. Ii then transports the nascent MHC II to more or less specialized compartment where they can load peptides derived from internalized pathogens.