Amyloid precursor-like protein 2 increases the endocytosis, instability, and turnover of the H2-K^d 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 Kd 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.