MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II COMPARTMENTS IN HUMAN B-LYMPHOBLASTOID-CELLS ARE DISTINCT FROM EARLY ENDOSOMES

In human B lymphoblastoid cell lines, the majority of major histocompa tibility complex (MHC) class II heterodimers are located on the cell s urface and in endocytic compartments, while invariant chain (Ii)-assoc iated class II molecules represent biosynthetic intermediates which ar e present mostly in the endoplasmic reticulum and Golgi complex. To in vestigate the origin of the MHC class II-positive compartments and the ir relation to early endosomes, the intracellular distribution of MHC class II molecules and Ii in relation to endocytic tracers was studied in human lymphoblastoid B cells by immunoelectronmicroscopy on ultrat hin cryosections. Cross-linking of surface immunoglobulins, followed b y a brief period of internalization of the immune complexes, did not a lter the intracellular distribution of MHC class II molecules. While e arly endosomes were abundantly labeled for the cross-linked immunoglob ulins, <1% of total MHC class II molecules were detectable in early en dosomes. MHC class II- and Ii-positive structures associated with the trans-Golgi network can be reached by endocytosed bovine serum albumin (BSA)-gold conjugates after 30 min of internalization. Prolonged expo sure to BSA-gold allowed visualization of later endocytic compartments , in which a progressive loss of Ii was observed: first the lumenal po rtion, and then the cytoplasmic portion of Ii escaped detection, culmi nating in the formation of MHC class II-positive compartments (MIIC) d evoid of Ii. The loss of Ii also correlated with a transition from a m ultivesicular to a multilaminar, electron-dense MIIC. The intracellula r compartments in which class II molecules reside (MIIC) are therefore a heterogeneous set of structures, part of the later aspects of the e ndocytic pathway.