The localization and intracellular transport of major histocompatibility complex 
(MHC) class II molecules nd lysosomal hydrolases were studied in I-Cell Disease 
(ICD) B lymphoblasts, which possess a mannose 6-phosphate (Man-6-P)-independent 
targeting pathway for lysosomal enzymes. In the trans-Golgi network (TGN), MHC 
class II-invariant chain complexes colocalized with the lysosomal hydrolase 
cathepsin D in buds and vesicles that lacked markers of clathrin-coated 
vesicle-mediated transport. These vesicles fused with the endocytic pathway 
leading to the formation of "early" MHC class II-rich compartments (MIICs). 
Similar structures were observed in the TGN of normal beta lymphoblasts although 
they were less abundant. Metabolic labeling and subcellular fractionation 
experiments indicated that newly synthesized cathepsin D and MHC class 
II-invariant chain complexes enter a non-clathrin-coated vesicular structure 
after their passage through the TGN and segregation from the secretory pathway. 
These vesicles were also devoid of the cation-dependent mannose 6-phosphate 
(Man-6-P) receptor, a marker of early and late endosomes. These findings suggest 
that in ICD B lymphoblasts the majority of MHC class II molecules are 
transported directly from the TGN to "early" MIICs and that acid hydrolases cam 
be incorporated into MIICs simultaneously by a Man-6-P-independant process.