Amyloid precursor-like protein 2 increases the endocytosis, instability and turnover of the H2-Kd MHC class I molecule

The defense against the invasion of viruses and tumors relies on the presentation of viral and tumor-derived peptides to CTL by cell surface MHC class I molecules. Previously, we showed that the ubiquitously expressed protein amyloid precursor-like protein 2 (APLP2) associates with the folded form of the MHC class I molecule K-d. In the current study, APLP2 was found to associate with folded K-d molecules following their endocytosis and to increase the amount of endocytosed K-d. In addition, increased expression of APLP2 was shown to decrease K-d surface expression and thermostability. Correspondingly, K-d thermostability and surface expression were increased by down-regulation of APLP2 expression. Overall, these data suggest that APLP2 modulates the stability and endocytosis of K-d molecules.