Invariant chain influences the immunological recognition of MHC class II molecules

Pro-B cells are early B-cell progenitors that retain macrophage potential. We have studied MHC class II molecules and invariant chain inducibility on four class II negative mouse pro- B-cell clones. We analyzed the effects of IL-4 and IFN-γ, which represent the major inducers of class II in the B-lymphoid and monocytic/macrophage lineages, respectively. After 48 h of treatment with either cytokine, three pro-B-cell clones (C2.13, A1.5, and F2.2) expressed intracellular invariant chain and cell-surface class II molecules. One clone (D2.1) remained negative. As already reported, more differentiated 70Z/3 pre-B cells were inducible by IL-4 only. These data suggest that the induction of class II and invariant-chain genes are subject to regulation throughout B-cell differentiation.

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Invariant Chain Expression Similarly Controls Presentation of Endogenously Synthesized and Exogenous Antigens by MHC Class II Molecules

Cellular Immunology ◽

10.1006/cimm.1993.1091 ◽

1993 ◽

Vol 148 (1) ◽

pp. 60-70 ◽

Cited By ~ 4

Author(s):

S. Lombard-Platet ◽

P. Bertolino ◽

C. Gimenez ◽

M. Humbert ◽

D. Gerlier ◽

...

Keyword(s):

Mhc Class Ii ◽

Class Ii ◽

Invariant Chain ◽

Mhc Class Ii Molecules

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Invariant chain p41 mediates production of soluble MHC class II molecules

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.12.106 ◽

2019 ◽

Vol 509 (1) ◽

pp. 216-221 ◽

Cited By ~ 1

Author(s):

Tatsuya Shishido ◽

Masako Kohyama ◽

Wataru Nakai ◽

Maki Matsumoto ◽

Haruhiko Miyata ◽

...

Keyword(s):

Mhc Class Ii ◽

Class Ii ◽

Invariant Chain ◽

Mhc Class Ii Molecules

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Sorting of MHC class II molecules and the associated invariant chain (Ii) in polarized MDCK cells

Journal of Cell Science ◽

10.1242/jcs.110.5.597 ◽

1997 ◽

Vol 110 (5) ◽

pp. 597-609 ◽

Cited By ~ 2

Author(s):

A. Simonsen ◽

E. Stang ◽

B. Bremnes ◽

M. Roe ◽

K. Prydz ◽

...

Keyword(s):

Epithelial Cells ◽

Antigen Presentation ◽

Mhc Class Ii ◽

Mdck Cells ◽

Intracellular Localization ◽

Cytoplasmic Tail ◽

Class Ii ◽

Invariant Chain ◽

Basolateral Targeting ◽

Mhc Class Ii Molecules

Epithelial cells have been found to express MHC class II molecules in vivo and are able to perform class II-restricted antigen presentation. The precise intracellular localization of these molecules in epithelial cells has been a matter of debate. We have analyzed the polarized targeting of human MHC class II molecules and the associated invariant chain (Ii) in stably transfected MDCK cells. The class II molecules are located at the basolateral surface and in intracellular vesicles, both when expressed alone or together with Ii. Ii is located in basolateral endosomes and can internalize through the basolateral plasma membrane domain. We show that the cytoplasmic tail of Ii contains information for basolateral targeting as it is sufficient to redirect the apical protein neuraminidase (NA) to the basolateral surface. We find that the two leucine-based motifs (LI and ML) in the cytoplasmic tail of Ii are individually sufficient for endosomal sorting and basolateral targeting of Ii in MDCK cells. In addition, basolateral sorting information is located within the 10 membrane-proximal residues of the Ii cytoplasmic tail. As several different signals mediate basolateral sorting of the class II/Ii complex, a polarized distribution of these molecules may be an essential feature of antigen presentation in epithelial cells.

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Secretory granules of mast cells accumulate mature and immature MHC class II molecules

Journal of Cell Science ◽

10.1242/jcs.114.2.323 ◽

2001 ◽

Vol 114 (2) ◽

pp. 323-334

Author(s):

H. Vincent-Schneider ◽

C. Thery ◽

D. Mazzeo ◽

D. Tenza ◽

G. Raposo ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Mhc Class Ii ◽

Cell Activation ◽

Secretory Granules ◽

Intracellular Localization ◽

Class Ii ◽

Mast Cell Activation ◽

Invariant Chain ◽

Mhc Class Ii Molecules

Bone marrow-derived mast cells as well as dendritic cells, macrophages and B lymphocytes express major histocompatibility complex (MHC) class II molecules. In mast cells, the majority of MHC class II molecules reside in intracellular cell type-specific compartments, secretory granules. To understand the molecular basis for the localisation of MHC class II molecules in secretory granules, MHC class II molecules were expressed, together with the invariant chain, in the mast cell line, RBL-2H3. Using electron and confocal microscopy, we observed that in RBL-2H3 cells, mature and immature class II molecules accumulate in secretory granules. Two particular features of class II transport accounted for this intracellular localization: first, a large fraction of newly synthesized MHC class II molecules remained associated with invariant chain fragments. This defect, resulting in a slower rate of MHC class II maturation, was ascribed to a low cathepsin S activity. Second, although a small fraction of class II dimers matured (i.e. became free of invariant chain), allowing their association with antigenic peptides, they were retained in secretory granules. As a consequence of this intracellular localization, cell surface expression of class II molecules was strongly increased by cell activation stimuli which induced the release of the contents of secretory granules. Our results suggest that antigen presentation, and thereby antigen specific T cell stimulation, are regulated in mast cells by stimuli which induce mast cell activation.

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

The Journal of Cell Biology ◽

10.1083/jcb.139.3.639 ◽

1997 ◽

Vol 139 (3) ◽

pp. 639-649 ◽

Cited By ~ 157

Author(s):

Monique J. Kleijmeer ◽

Stanislaw Morkowski ◽

Janice M. Griffith ◽

Alexander Y. Rudensky ◽

Hans J. Geuze

Keyword(s):

Major Histocompatibility Complex ◽

B Cells ◽

Mhc Class Ii ◽

Class Ii ◽

Invariant Chain ◽

Histocompatibility Complex ◽

Peptide Complexes ◽

Endocytic Compartments ◽

Human And Mouse ◽

Mhc Class Ii Molecules

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.

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Distinct Intracellular Compartments Involved in Invariant Chain Degradation and Antigenic Peptide Loading of Major Histocompatibility Complex (MHC) Class II Molecules

The Journal of Cell Biology ◽

10.1083/jcb.139.6.1433 ◽

1997 ◽

Vol 139 (6) ◽

pp. 1433-1446 ◽

Cited By ~ 45

Author(s):

Giorgio Ferrari ◽

Andrew M. Knight ◽

Colin Watts ◽

Jean Pieters

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class Ii ◽

Human Leukocyte ◽

Subcellular Location ◽

Class Ii ◽

Invariant Chain ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Peptide Loading ◽

Mhc Class Ii Molecules

Major histocompatibility complex (MHC) class II molecules are transported to intracellular MHC class II compartments via a transient association with the invariant chain (Ii). After removal of the invariant chain, peptides can be loaded onto class II molecules, a process catalyzed by human leukocyte antigen-DM (HLA-DM) molecules. Here we show that MHC class II compartments consist of two physically and functionally distinct organelles. Newly synthesized MHC class II/Ii complexes were targeted to endocytic organelles lacking HLA-DM molecules, where Ii degradation occurred. From these organelles, class II molecules were transported to a distinct organelle containing HLA-DM, in which peptides were loaded onto class II molecules. This latter organelle was not directly accessible via fluid phase endocytosis, suggesting that it is not part of the endosomal pathway. Uptake via antigen-specific membrane immunoglobulin resulted however in small amounts of antigen in the HLA-DM positive organelles. From this peptide-loading compartment, class II–peptide complexes were transported to the plasma membrane, in part after transit through endocytic organelles. The existence of two separate compartments, one involved in Ii removal and the other functioning in HLA-DM–dependent peptide loading of class II molecules, may contribute to the efficiency of antigen presentation by the selective recruitment of peptide-receptive MHC class II molecules and HLA-DM to the same subcellular location.

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