Endocytosis and Biosynthetic Transport of Murine MHC Class II Molecules in Antigen Presenting Cells

Abstract

In B lymphocytes, the processing of exogenous proteins and the subsequent binding of antigenic peptides to MHC class II molecules occurs most likely within endocytic compartments. Using various biochemical and morphological techniques, we show that the endosomal compartments are loaded with a pool of MHC class II molecules which are permanently endocytosed and recycled to the cell surface in murine B lymphoma cells. L fibroblasts transfected with I-A _αβ ^K or I-E _α ^K _β ^K/d fail to internalize their surface class II molecules even when expressed in conjunction with the class II associated invariant chain (Ii). We suggest that in murine B lymphoma cells, antigenic peptides can gain access to a pool of recycling class II molecules whereas in L cells they meet newly synthesized class II molecules targeted to the endosomal compartments. In B lymphocytes and macrophages, the invariant chain (Ii) is synthesized in large excess with respect to MHC class II α and β chains. Ii binds to MHC class II molecules in endoplasmic reticulum and is partially degraded presumably at the level of the trans-Golgi network or of prelysosomal compartments. To estimate the role fo Ii molecules in the function and the transport of class II molecules, we have surtransfected murine L fibroblasts expressing IAk molecules using as controls L fibroblasts expressing only IA^k or Ii. As pointed out before for the presentation of cytochrome B5 in the context of IE^k (Stockinger et al., 1989 Cell 56, 683–689) we found that Ii expression enhance by a hundred fold the capacity of IA^k positive L cell to present hen egg lysozyme.