Mouse B lymphocyte specific endocytosis and recycling of MHC class II molecules.

Abstract

In B lymphocytes, the processing of exogenous proteins and the subsequent binding of antigenic peptides to class II molecules encoded by the major histocompatibility complex (MHC) occurs most likely within endocytic compartments. To examine the endocytic transport of MHC class II molecules, we used (i) surface iodination followed by internalization, pronase treatment and immunoprecipitation, (ii) in situ iodination of endosomal compartments, and (iii) confocal microscopy to visualize the fate of fluorescence coupled Fab fragments. In murine I‐Ak, I‐Ek positive B lymphoma cells, cell surface MHC class II molecules are partially protected from pronase digestion after 15 min at 37 degrees C and recycled back to the cell surface within the next 30 min. The fluorescence coupled Fab fragments are delivered to juxtanuclear endocytic compartments in 15 min. In contrast to the murine B cells, L fibroblasts transfected with either I‐A alpha beta k or I‐E alpha k beta k,d fail to internalize their surface class II molecules. A fraction of class II molecules, however, is still present in endosomal compartments as detected after in situ iodination in L fibroblasts. We conclude that the recipient L fibroblasts lack one or several factors needed for the transport of MHC class II molecules from the cell surface to the endosomes. 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.

B Cell Receptors and Complement Receptors Target the Antigen to Distinct Intracellular Compartments

“…MHC-II-peptide complexes are then exported to the plasma membrane. Surface class II molecules can be reinternalized into early endosomes (16), where they may exchange their peptide and then recycle to the plasma membrane (17). Some peptides rapidly generated in the endocytic pathway are presented by these recycling class II molecules (18).…”

Abundant empty class II MHC molecules on the surface of immature dendritic cells

“…MHC-Ii complexes transport to early endosomal compartments under the influence of a dileucine sorting signal on the Ii cytoplasmic tail (3), either directly from the trans-Golgi network or alternately after transient expression on the cell membrane and rapid internalization (5). MHC-Ii complexes traverse the endocytic pathway from early to late endosomes and finally into lysosomes (6). In these compartments, bound Ii is degraded by cathepsins and other endosomal proteases, leaving a small fragment (CLIP) bound in the MHC peptide-binding groove (7,8).…”

“…In DC from mice deficient in Ii, normal levels of cell-surface class II MHC are expressed, whereas in B cells, expression is significantly reduced (17). In DC, the majority of nascent class II MHC-Ii complexes transport to the cell surface en route to endocytic compartments, whereas in B cells this is a minor pathway (6). Finally, class II MHC can access a nonacidic early endosomal compartment used for antigen storage in DC that has not been observed in B cells (18).…”

Dendritic cell maturation and antigen presentation in the absence of invariant chain

“…The intracellular route followed by class II-Ii complexes from the trans-Golgi network to the endocytic pathway remains so far poorly characterized. Among the different models, an initial targeting to early endosomes, possibly via the plasma membrane, has been proposed (1- 4,12,17,[21][22][23]. A dileucine targeting motif in the cytoplasmic tail of Ii plays a pivotal role in the control of the movements of class II-Ii complexes through the endocytic pathway (for review, see ref.…”