scholarly journals Vaccinia virus decreases major histocompatibility complex (MHC) class II antigen presentation, T-cell priming, and peptide association with MHC class II

Immunology ◽  
2009 ◽  
Vol 128 (3) ◽  
pp. 381-392 ◽  
Author(s):  
Kristina E. Rehm ◽  
Ramsey F. Connor ◽  
Gwendolyn J. B. Jones ◽  
Kenneth Yimbu ◽  
Mark D. Mannie ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Vaccinia Virus ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Histocompatibility Complex ◽  
T Cell Priming ◽  
Class Ii Antigen ◽  
Mhc Class Ii Antigen

scholarly journals Alternative Endogenous Protein Processing via an Autophagy-Dependent Pathway Compensates for Yersinia-Mediated Inhibition of Endosomal Major Histocompatibility Complex Class II Antigen Presentation

2010 ◽  
Vol 78 (12) ◽  
pp. 5138-5150 ◽  
Author(s):  
Holger Rüssmann ◽  
Klaus Panthel ◽  
Brigitte Köhn ◽  
Stefan Jellbauer ◽  
Sebastian E. Winter ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Virulence Factors ◽  
Antigen Processing ◽  
Class Ii ◽  
T Cell Response ◽  
Histocompatibility Complex ◽  
Class Ii Antigen ◽  
Mhc Class Ii Antigen

ABSTRACT Extracellular Yersinia pseudotuberculosis employs a type III secretion system (T3SS) for translocating virulence factors (Yersinia outer proteins [Yops]) directly into the cytosol of eukaryotic cells. Recently, we used YopE as a carrier molecule for T3SS-dependent secretion and translocation of listeriolysin O (LLO) from Listeria monocytogenes. We demonstrated that translocation of chimeric YopE/LLO into the cytosol of macrophages by Yersinia results in the induction of a codominant antigen-specific CD4 and CD8 T-cell response in orally immunized mice. In this study, we addressed the requirements for processing and major histocompatibility complex (MHC) class II presentation of chimeric YopE proteins translocated into the cytosol of macrophages by the Yersinia T3SS. Our data demonstrate the ability of Yersinia to counteract exogenous MHC class II antigen presentation of secreted hybrid YopE by the action of wild-type YopE and YopH. In the absence of exogenous MHC class II antigen presentation, an alternative pathway was identified for YopE fusion proteins originating in the cytosol. This endogenous antigen-processing pathway was sensitive to inhibitors of phagolysosomal acidification and macroautophagy, but it did not require the function either of the proteasome or of transporters associated with antigen processing. Thus, by an autophagy-dependent mechanism, macrophages are able to compensate for the YopE/YopH-mediated inhibition of the endosomal MHC class II antigen presentation pathway for exogenous antigens. This is the first report demonstrating that autophagy might enable the host to mount an MHC class II-restricted CD4 T-cell response against translocated bacterial virulence factors. We provide critical new insights into the interaction between the mammalian immune system and a human pathogen.

scholarly journals Deficient Major Histocompatibility Complex Class II Antigen Presentation in a Subset of Hodgkin's Disease Tumor Cells

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2252-2259 ◽  
Author(s):  
Herbert Bosshart ◽  
Ruth F. Jarrett
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Tumor Cells ◽  
Mhc Class Ii ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Class Ii ◽  
Histocompatibility Complex ◽  
Class Ii Antigen ◽  
Mhc Class Ii Molecules

Abstract Hodgkin's disease is a common malignancy of the lymphoid system. Although the scarce Hodgkin and Reed-Sternberg (HRS) tumor cells in involved tissue synthesize major histocompatibility complex (MHC) class II and costimulatory molecules such as CD40 or CD86, it is unclear whether these tumor cells are operational antigen-presenting cells (APC). We developed an immunofluorescence-based assay to determine the number of MHC class II molecules present on the surface of single living HRS cells. We found that in fresh Hodgkin's disease lymph node biopsies, a subset of HRS cells express a substantial number of surface MHC class II molecules that are occupied by MHC class II–associated invariant chain peptides (CLIP), indicating deficient loading of MHC class II molecules with antigenic peptides. Cultured Hodgkin's disease–derived (HD) cell lines, however, were found to express few MHC class II molecules carrying CLIP peptides on the cell surface and were shown to generate sodium dodecyl sulphate (SDS)-stable MHC class II αβ dimers. In addition to showing deficient MHC class II antigen presentation in a subset of HRS cells, our results show that the widely used HD-cell lines are not ideal in vitro models for the disease. The disruption of MHC class II–restricted antigen presentation in HRS cells could represent a key mechanism by which these tumor cells escape immune surveillance.

The FcγRIa (CD64) Ligand Binding Chain Triggers Major Histocompatibility Complex Class II Antigen Presentation Independently of Its Associated FcR γ-Chain

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 808-817 ◽  
Author(s):  
Martine J. van Vugt ◽  
Monique J. Kleijmeer ◽  
Tibor Keler ◽  
Ingrid Zeelenberg ◽  
Marc A. van Dijk ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Ligand Binding ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Cytoplasmic Tail ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Rabbit Igg ◽  
Class Ii Antigen

Abstract Within multi-subunit Ig receptors, the FcR γ-chain immunoreceptor tyrosine-based activation motif (ITAM) plays a crucial role in enabling antigen presentation. This process involves antigen-capture and targeting to specific degradation and major histocompatibility complex (MHC) class II loading compartments. Antigenic epitopes are then presented by MHC class II molecules to specific T cells. The high-affinity receptor for IgG, hFcγRIa, is exclusively expressed on myeloid lineage cells and depends on the FcR γ-chain for surface expression, efficient ligand binding, and most phagocytic effector functions. However, we show in this report, using the IIA1.6 cell model, that hFcγRIa can potentiate MHC class II antigen presentation, independently of a functional FcR γ-chain ITAM. Immunoelectron microscopic analyses documented hFcγRIa -chain/rabbit IgG-Ovalbumin complexes to be internalized and to migrate via sorting endosomes to MHC class II-containing late endosomes. Radical deletion of the hFcγRIa -chain cytoplasmic tail did not affect internalization of rabbit IgG-Ovalbumin complexes. Importantly, however, this resulted in diversion of receptor-ligand complexes to the recycling pathway and decreased antigen presentation. These results show the hFcγRIa cytoplasmic tail to contain autonomous targeting information for intracellular trafficking of receptor-antigen complexes, although deficient in canonical tyrosine- or dileucine-targeting motifs. This is the first documentation of autonomous targeting by a member of the multichain FcR family that may critically impact the immunoregulatory role proposed for hFcγRIa (CD64).

scholarly journals Vaccinia virus A35R inhibits MHC class II antigen presentation

Virology ◽  
2010 ◽  
Vol 397 (1) ◽  
pp. 176-186 ◽  
Author(s):  
Kristina E. Rehm ◽  
Ramsey F. Connor ◽  
Gwendolyn J.B. Jones ◽  
Kenneth Yimbu ◽  
Rachel L. Roper
Keyword(s):  
Vaccinia Virus ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class Ii Antigen ◽  
Mhc Class Ii Antigen

scholarly journals Syk Tyrosine Kinase and B Cell Antigen Receptor (BCR) Immunoglobulin-α Subunit Determine BCR-mediated Major Histocompatibility Complex Class II–restricted Antigen Presentation

1998 ◽  
Vol 188 (5) ◽  
pp. 819-831 ◽  
Author(s):  
Danielle Lankar ◽  
Volker Briken ◽  
Kristin Adler ◽  
Peter Weiser ◽  
Sylvanie Cassard ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Cell Epitopes ◽  
Major Histocompatibility ◽  
Α Subunit ◽  
Histocompatibility Complex

Stimulation of CD4+ helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptides which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes mediate efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of membrane immunoglobulin (Ig) associated with Ig-α/Ig-β heterodimers which, second, target antigens to MHC class II–containing compartments. We report that antigen internalization and antigen targeting through the BCR or its Ig-α–associated subunit to newly synthesized class II lead to the presentation of a large spectrum of T cell epitopes, including some cryptic T cell epitopes. To further characterize the intracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-α cytoplasmic tail, and overexpression in B cells of dominant negative syk mutants. Thus, we found that the syk tyrosine kinase, an effector of the BCR signal transduction pathway, is involved in the presentation of peptide– MHC class II complexes through antigen targeting by BCR subunits.

scholarly journals Deficient Major Histocompatibility Complex Class II Antigen Presentation in a Subset of Hodgkin's Disease Tumor Cells

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2252-2259 ◽  
Author(s):  
Herbert Bosshart ◽  
Ruth F. Jarrett
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Tumor Cells ◽  
Mhc Class Ii ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Class Ii ◽  
Histocompatibility Complex ◽  
Class Ii Antigen ◽  
Mhc Class Ii Molecules

Hodgkin's disease is a common malignancy of the lymphoid system. Although the scarce Hodgkin and Reed-Sternberg (HRS) tumor cells in involved tissue synthesize major histocompatibility complex (MHC) class II and costimulatory molecules such as CD40 or CD86, it is unclear whether these tumor cells are operational antigen-presenting cells (APC). We developed an immunofluorescence-based assay to determine the number of MHC class II molecules present on the surface of single living HRS cells. We found that in fresh Hodgkin's disease lymph node biopsies, a subset of HRS cells express a substantial number of surface MHC class II molecules that are occupied by MHC class II–associated invariant chain peptides (CLIP), indicating deficient loading of MHC class II molecules with antigenic peptides. Cultured Hodgkin's disease–derived (HD) cell lines, however, were found to express few MHC class II molecules carrying CLIP peptides on the cell surface and were shown to generate sodium dodecyl sulphate (SDS)-stable MHC class II αβ dimers. In addition to showing deficient MHC class II antigen presentation in a subset of HRS cells, our results show that the widely used HD-cell lines are not ideal in vitro models for the disease. The disruption of MHC class II–restricted antigen presentation in HRS cells could represent a key mechanism by which these tumor cells escape immune surveillance.

Sign in / Sign up

Export Citation Format

Share Document