The cytoplasmic tail of invariant chain modulates antigen processing and presentation

The MHC class II-associated invariant chain (Ii) has several important functions in antigen presentation. In this study, we have examined the effect of lip33 expression on endocytic transport and antigen presentation. We find that degradation of both endocytosed antigen and li itself is delayed in cells expressing high levels of Ii, whereas a mutant Ii with an altered charge distribution in the cytoplasmic tail was unable to exert this effect. Furthermore, the Ii mutant did not enhance the presentation of an li-dependent MHC class II-restricted epitope to the same extent as the wild type. In a parallel study, we investigated the effect of charge in the cytoplasmic tail of Ii. We find that due to exposed negative charges, it promotes endosome fusion events, and we suggest that this causes endosomal retention (Nordeng et al., Mol. Biol. Cell 2002). Together, the data reveal an additional property of the lip33 cytoplasmic tail that contributes to the modulation of antigen processing and presentation.