Invariant chain increases the half-life of MHC II by delaying endosomal maturation

Mounting adaptive immune responses requires the cell surface expression of major histocompatibility class II molecules (MHC II) loaded with antigenic peptide. However, in the absence of antigenic stimuli, the surface population of MHC II is highly dynamic and exhibits a high turnover. Several studies have focused on the regulation of MHC II, and it is now recognized that ubiquitination is one key mechanism operating in the turnover of MHC II in B cells and dendritic cells. Here, we describe how the invariant chain (Ii) can prolong the half-life of MHC II through its action on the endocytic pathway. We find that in cells expressing intermediate-to-high levels of Ii, the half-life of MHC II is increased, with MHC II accumulating in slowly-maturing endosomes. The accumulation in endosomes is not due to retention of new MHC II directed from the endoplasmatic reticulum, as also mature, not Ii associated, MHC II is preserved. We suggest that this alternative endocytic pathway induced by Ii would serve to enhance the rate, quantity and diversity of MHC II antigen presentation by concentrating MHC II into specialized compartments and reducing the need for new MHC II synthesis upon antigen encounter.