Cross-linking of MHC class II molecules interferes with phorbol 12,13-dibutyrate-induced differentiation of resting B cells by inhibiting Rac-associated ROS-dependent ERK/p38 MAP kinase pathways leading to NF-κB activation

2007 ◽  
Vol 44 (7) ◽  
pp. 1577-1586 ◽  
Author(s):  
Hee-Young Yang ◽  
Ju Kim ◽  
Gook-Hyun Chung ◽  
Jeong-Chae Lee ◽  
Yong-Suk Jang
Keyword(s):  
B Cells ◽  
Map Kinase ◽  
Mhc Class Ii ◽  
Class Ii ◽  
P38 Map Kinase ◽  
Cross Linking ◽  
Induced Differentiation ◽  
Map Kinase Pathways ◽  
Mhc Class Ii Molecules

scholarly journals Early Endosomes Are Required for Major Histocompatiblity Complex Class II Transport to Peptide-loading Compartments

1999 ◽  
Vol 10 (9) ◽  
pp. 2891-2904 ◽  
Author(s):  
Valérie Brachet ◽  
Gérard Péhau-Arnaudet ◽  
Catherine Desaymard ◽  
Graça Raposo ◽  
Sebastian Amigorena
Keyword(s):  
Mhc Class Ii ◽  
Class Ii ◽  
Endocytic Pathway ◽  
Cross Linking ◽  
Histocompatibility Complex ◽  
Early Endosomes ◽  
Peptide Loading ◽  
Golgi Network ◽  
Mhc Class Ii Molecules

Antigen presentation to CD4+ T lymphocytes requires transport of newly synthesized major histocompatibility complex (MHC) class II molecules to the endocytic pathway, where peptide loading occurs. This step is mediated by a signal located in the cytoplasmic tail of the MHC class II-associated Ii chain, which directs the MHC class II-Ii complexes from the trans-Golgi network (TGN) to endosomes. The subcellular machinery responsible for the specific targeting of MHC class II molecules to the endocytic pathway, as well as the first compartments these molecules enter after exit from the TGN, remain unclear. We have designed an original experimental approach to selectively analyze this step of MHC class II transport. Newly synthesized MHC class II molecules were caused to accumulate in the Golgi apparatus and TGN by incubating the cells at 19°C, and early endosomes were functionally inactivated by in vivo cross-linking of transferrin (Tf) receptor–containing endosomes using Tf-HRP complexes and the HRP-insoluble substrate diaminobenzidine. Inactivation of Tf-containing endosomes caused a marked delay in Ii chain degradation, peptide loading, and MHC class II transport to the cell surface. Thus, early endosomes appear to be required for delivery of MHC class II molecules to the endocytic pathway. Under cross-linking conditions, most αβIi complexes accumulated in tubules and vesicles devoid of γ-adaptin and/or mannose-6-phosphate receptor, suggesting an AP1-independent pathway for the delivery of newly synthesized MHC class II molecules from the TGN to endosomes.

scholarly journals Cross-linking of major histocompatibility complex class II molecules by staphylococcal enterotoxin A superantigen is a requirement for inflammatory cytokine gene expression.

1995 ◽  
Vol 182 (5) ◽  
pp. 1573-1577 ◽  
Author(s):  
K Mehindate ◽  
J Thibodeau ◽  
M Dohlsten ◽  
T Kalland ◽  
R P Sékaly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mhc Class Ii ◽  
Messenger Rna ◽  
Class Ii ◽  
Cytokine Gene Expression ◽  
Cross Linking ◽  
Staphylococcal Enterotoxin A ◽  
Cytokine Gene ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Molecules

Staphylococcal enterotoxin A (SEA) has two distinct binding sites for major histocompatibility complex (MHC) class II molecules. The aspartic acid located at position 227 (D227) in the COOH terminus of SEA is one of the three residues involved in its interaction with the DR beta chain, whereas the phenylalanine 47 (F47) of the NH2 terminus is critical for its binding to the DR alpha chain. Upon interaction with MHC class II molecules, SEA triggers several cellular events leading to cytokine gene expression. In the present study, we have demonstrated that, contrary to wild-type SEA, stimulation of the THP1 monocytic cell line with SEA mutated at position 47 (SEAF47A) or at position 227 (SEAD227A) failed to induce interleukin 1 beta and tumor necrosis factor-alpha messenger RNA expression. Pretreatment of the cells with a 10-fold excess of either SEAF47A or SEAD227A prevented the increase in cytokine messenger RNA induced by wild-type SEA. However, cross-linking of SEAF47A or SEAD227A bound to MHC class II molecules with F(ab')2 anti-SEA mAb leads to cytokine gene expression, whereas cross-linking with F(ab) fragments had no effect. Taken together, these results indicate that cross-linking of two MHC class II molecules by one single SEA molecule is a requirement for cytokine gene expression.

scholarly journals Both IFN-γ and IL-4 Induce MHC Class II Expression at the Surface of Mouse Pro-B Cells

1997 ◽  
Vol 5 (2) ◽  
pp. 115-120 ◽  
Author(s):  
Suzanne Lombard-Platet ◽  
Valerie Meyer ◽  
Rhodri Ceredig
Keyword(s):  
B Cells ◽  
B Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Invariant Chain ◽  
B Cell Differentiation ◽  
Cell Clones ◽  
Ifn Γ ◽  
B Lymphoid ◽  
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.

scholarly journals CD4+ T cell responses in mice lacking MHC class II molecules specifically on B cells

1998 ◽  
Vol 28 (11) ◽  
pp. 3763-3772 ◽  
Author(s):  
G. Stuart Williams ◽  
Annette Oxenius ◽  
Hans Hengartner ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
T Cell ◽  
B Cells ◽  
Mhc Class Ii ◽  
T Cell Responses ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Mhc Class Ii Molecules

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

1997 ◽  
Vol 139 (3) ◽  
pp. 639-649 ◽  
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.

scholarly journals The protein tyrosine kinase p56lck regulates cell adhesion mediated by CD4 and major histocompatibility complex class II proteins.

1994 ◽  
Vol 180 (5) ◽  
pp. 1729-1739 ◽  
Author(s):  
M S Kinch ◽  
A Sanfridson ◽  
C Doyle
Keyword(s):  
Cell Adhesion ◽  
B Cells ◽  
Tyrosine Kinase ◽  
Mhc Class Ii ◽  
Kinase Activity ◽  
Class Ii ◽  
Wild Type ◽  
Tyrosine Kinase Activity ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Molecules

The CD4 protein is expressed on a subset of human T lymphocytes that recognize antigen in the context of major histocompatibility complex (MHC) class II molecules. Using Chinese hamster ovary (CHO) cells expressing human CD4, we have previously demonstrated that the CD4 protein can mediate cell adhesion by direct interaction with MHC class II molecules. In T lymphocytes, CD4 can also function as a signaling molecule, presumably through its intracellular association with p56lck, a member of the src family of protein tyrosine kinases. In the present report, we show that p56lck can affect cell adhesion mediated by CD4 and MHC class II molecules. The expression of wild-type p56lck in CHO-CD4 cells augments the binding of MHC class II+ B cells, whereas the expression of a mutant p56lck protein with elevated tyrosine kinase activity results in decreased binding of MHC class II+ B cells. Using site-specific mutants of p56lck, we demonstrate that the both the enzymatic activity of p56lck and its association with CD4 are required for this effect on CD4/MHC class II adhesion. Further, the binding of MHC class II+ B cells induces CD4 at the cell surface to become organized into structures resembling adhesions-type junctions. Both wild-type and mutant forms of p56lck influence CD4-mediated adhesion by regulating the formation of these structures. The wild-type lck protein enhances CD4/MHC class II adhesion by augmenting the formation of CD4-associated adherens junctions whereas the elevated tyrosine kinase activity of the mutant p56lck decreases CD4-mediated cell adhesion by preventing the formation of these structures.

Sign in / Sign up

Export Citation Format

Share Document