Major Histocompatibility Complex Class II Compartments in Human and Mouse B Lymphoblasts Represent Conventional Endocytic Compartments

Abstract

In most human and mouse antigen-presenting cells, the majority of intracellular major histocompatibility complex (MHC) class II molecules resides in late endocytic MHC class II compartments (MIICs), thought to function in antigen processing and peptide loading. However, in mouse A20 B cells, early endocytic class II-containing vesicles (CIIVs) have been reported to contain most of the intracellular MHC class II molecules and have also been implicated in formation of MHC class II–peptide complexes. To address this discrepancy, we have studied in great detail the endocytic pathways of both a human (6H5.DM) and a mouse (A20.Ab) B cell line. Using quantitative immunoelectron microscopy on cryosections of cells that had been pulse–chased with transferrin-HRP or BSA-gold as endocytic tracers, we have identified up to six endocytic subcompartments including an early MIIC type enriched in invariant chain, suggesting that it serves as an important entrance to the endocytic pathway for newly synthesized MHC class II/invariant chain complexes. In addition, early MIICs represented the earliest endocytic compartment containing MHC class II– peptide complexes, as shown by using an antibody against an abundant endogenous class II–peptide complex. The early MIIC exhibited several though not all of the characteristics reported for the CIIV and was situated just downstream of early endosomes. We have not encountered any special class II-containing endocytic structures besides those normally present in nonantigen-presenting cells. Our results therefore suggest that B cells use conventional endocytic compartments rather than having developed a unique compartment to accomplish MHC class II presentation.

Brucella abortus Lipopolysaccharide in Murine Peritoneal Macrophages Acts as a Down-Regulator of T Cell Activation

“…In APCs, association of antigenic peptides with MHC class II molecules can occur in different compartments of the endocytic pathway (26). For instance, the HEL 46 -61 epitope requires newly synthesized MHC class II molecules and the invariant chain expression to be presented to 3A9 hybridoma cells and has been shown to associate with class II molecules inside late endocytic compartments.…”

Receptor-Facilitated Antigen Presentation Requires the Recruitment of B Cell Linker Protein to Igα

“…The best described of these is the MHC class II-enriched compartment (MIIC), which in murine B cells is multivesicular (7), lysosome-associated membrane protein-1 ϩ (Lamp-1 ϩ ), MHC class II ϩ (8), H2-M ϩ , transferrin receptor (TfR) Ϫ , and M6PR Ϫ (9 -13). In this compartment, MHC class II molecules loaded with specific peptides are first detected following antigenic recognition by the BCR (8).…”

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

“…In professional antigen-presenting cells, the organelles at which MHCII peptide loading occurs mainly constitute late endosomes, although lysosomes have also been implicated (Geuze 1998). Together, these endocytic compartments are also referred to as MHCII compartments (MIICs) (Peters et al 1991;Kleijmeer et al 1997Kleijmeer et al , 2001). DCs constitutively synthesize MHCII, which, in the absence of pathogen, are all loaded with "self " peptides in MIICs.…”