scholarly journals Polarized Expression of CD74 by Gastric Epithelial Cells

2005 ◽  
Vol 53 (12) ◽  
pp. 1481-1489 ◽  
Author(s):  
Carlos A. Barrera ◽  
Ellen J. Beswick ◽  
Johanna C. Sierra ◽  
David Bland ◽  
Rosario Espejo ◽  
...  

CD74 is known as the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) that regulates the cell biology and functions of MHC class II molecules. Class II MHC and Ii expression was believed to be restricted to classical antigen-presenting cells (APC); however, during inflammation, other cell types, including mucosal epithelial cells, have also been reported to express class II MHC molecules. Given the importance of Ii in the biology of class II MHC, we sought to examine the expression of Ii by gastric epithelial cells (GEC) to determine whether class II MHC molecules in these nonconventional APC cells were under the control of Ii and to further support the role that these cells may play in local immune and inflammatory responses during Helicobacter pylori infection. Thus we examined the expression of Ii on GEC from human biopsy samples and then confirmed this observation using independent methods on several GEC lines. The mRNA for Ii was detected by RT-PCR, and the various protein isoforms were also detected. Interestingly, these cells have a high level expression of surface Ii, which is polarized to the apical surface. These studies are the first to demonstrate the constitutive expression of Ii by human GEC.

1998 ◽  
Vol 187 (10) ◽  
pp. 1659-1669 ◽  
Author(s):  
Xuejun Fan ◽  
Sheila E. Crowe ◽  
Simon Behar ◽  
Harshani Gunasena ◽  
Gang Ye ◽  
...  

Helicobacter pylori infection is associated with gastric epithelial damage, including apoptosis, ulceration, and cancer. Although bacterial factors and the host response are believed to contribute to gastric disease, no receptor has been identified that explains how the bacteria attach and signal the host cell to undergo apoptosis. Using H. pylori as “bait” to capture receptor proteins in solubilized membranes of gastric epithelial cells, class II major histocompatibility complex (MHC) molecules were identified as a possible receptor. Signaling through class II MHC molecules leading to the induction of apoptosis was confirmed using cross-linking IgM antibodies to surface class II MHC molecules. Moreover, binding of H. pylori and the induction of apoptosis were inhibited by antibodies recognizing class II MHC. Since type 1 T helper cells are present during infection and produce interferon (IFN)-γ, which increases class II MHC expression, gastric epithelial cell lines were exposed to H. pylori in the presence or absence of IFN-γ. IFN-γ increased the attachment of the bacteria as well as the induction of apoptosis in gastric epithelial cells. In contrast to MHC II–negative cell lines, H. pylori induced apoptosis in cells expressing class II MHC molecules constitutively or after gene transfection. These data describe a novel receptor for H. pylori and provide a mechanism by which bacteria and the host response interact in the pathogenesis of gastric epithelial cell damage.


1998 ◽  
Vol 114 ◽  
pp. A118 ◽  
Author(s):  
X.J. Fan ◽  
H. Gunasena ◽  
M. Gonzales ◽  
R. Almanza ◽  
Z. Cheng ◽  
...  

2020 ◽  
Vol 8 (3) ◽  
pp. 144-156
Author(s):  
Şule KARATAŞ ◽  
Fatma SAVRAN OĞUZ

Introduction: Peptides obtained by processing intracellular and extracellular antigens are presented to T cells to stimulate the immune response. This presentation is made by peptide receptors called major histocompatibility complex (MHC) molecules. The regulation mechanisms of MHC molecules, which have similar roles in the immune response, especially at the gene level, have significant differences according to their class. Objective: Class I and class II MHC molecules encoded by MHC genes on the short arm of the sixth chromosome are peptide receptors that stimulate T cell response. These peptides, which will enable the recognition of the antigen from which they originate, are loaded into MHC molecules and presented to T cells. Although the principles of loading and delivering peptides are similar for both molecules, the peptide sources and peptide loading mechanisms are different. In addition, class I molecules are expressed in all nucleated cells while class II molecules are expressed only in Antigen Presentation Cells (APC). These differences; It shows that MHC class I is not expressed by exactly the same transcriptional mechanisms as MHC class II. In our article, we aimed to compare the gene expressions of both classes and reveal their similarities and differences. Discussion and Conclusion: A better understanding of the transcriptional mechanisms of MHC molecules will reveal the role of these molecules in diseases more clearly. In our review, we discussed MHC gene regulation mechanisms with presence of existing informations, which is specific to the MHC class, for contribute to future research. Keywords: MHC class I, MHC class II, MHC gene regulation, promoter, SXY module, transcription


2012 ◽  
Vol 60 (1) ◽  
pp. 1 ◽  
Author(s):  
Sarah E. Jobbins ◽  
Claire E. Sanderson ◽  
Joanna E. Griffith ◽  
Mark B. Krockenberger ◽  
Katherine Belov ◽  
...  

The host immune response is an important factor determining the outcome of the host–pathogen–environment interaction. At the gateway between the innate and adaptive immune systems are MHC molecules, which facilitate antigen presentation to T lymphocytes, and initiate the adaptive immune response. Despite their integral role in adaptive immunity, the genes encoding class II MHC molecules have not been examined directly in koalas. Furthermore, indirect historical evidence suggests that this species might lack functional diversity in class II MHC genes, with potential implications for disease susceptibility. We have examined diversity in the β chain genes of the koala class II MHC DA gene family and identified 23 alleles, including several atypical alleles. The levels of diversity observed are consistent with other marsupial and eutherian species, and do not support the paucity of variation suggested by the early literature. These findings are relevant to the conservation management of koalas and provide both a benchmark for maintaining population diversity and a platform for further conservation genetic research in this species.


2002 ◽  
Vol 63 (5) ◽  
pp. 384-393 ◽  
Author(s):  
Carlos Barrera ◽  
Rosario Espejo ◽  
Victor E Reyes

2005 ◽  
Vol 73 (5) ◽  
pp. 2736-2743 ◽  
Author(s):  
Ellen J. Beswick ◽  
David A. Bland ◽  
Giovanni Suarez ◽  
Carlos A. Barrera ◽  
Xuejung Fan ◽  
...  

ABSTRACT The pathogenesis associated with Helicobacter pylori infection requires consistent contact with the gastric epithelium. Although several cell surface receptors have been suggested to play a role in adhesion, the bacterium-host interactions that elicit host responses are not well defined. This study investigated the interaction of H. pylori with the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells. Bacterial binding was increased when CD74 surface expression was increased by gamma interferon (IFN-γ) treatment or by fibroblast cells transfected with CD74, while binding was decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated bacteria. H. pylori was also shown to bind directly to affinity-purified CD74 in the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74 were verified to stimulate IL-8 production by unrelated cell lines expressing CD74 in the absence of class II MHC. Increased CD74 expression by cells increased IL-8 production in response to H. pylori, and agents that block CD74 decreased these responses. The binding of H. pylori to CD74 presents a novel insight into an initial interaction of H. pylori with the gastric epithelium that leads to upregulation of inflammatory responses.


2000 ◽  
Vol 165 (4) ◽  
pp. 1918-1924 ◽  
Author(s):  
Xuejun Fan ◽  
Harshani Gunasena ◽  
Zhijei Cheng ◽  
Rosario Espejo ◽  
Sheila E. Crowe ◽  
...  

1990 ◽  
Vol 4 (7) ◽  
pp. 267-270 ◽  
Author(s):  
W Doe ◽  
P Pavli

The induction of T cell responses requires recognition of antigens in association with class II major histocompatibility complex (MHC) proteins and specialized antigen-presenting cells. Candidate antigen-presenting cells in the gut include dendritic cells, macrophages, B lymphocytes, mucosal epithelial cells and endothelial cells. Dendritic cells isolated from normal human colon are potent inducers of primary immune responses and express high levels of class lI MHC proteins. Lamina propria macrophages display class II MHC proteins, can present antigens to sensitized T cells, may process antigen and release interleukin-l, but suppress antigen presentation by intestinal dendritic cells in a dose-dependent manner. Class II MHC molecules are normally expressed on small intestinal epithelial cells but not on normal colonic epithelial cells. Suppressor T cells and unresponsive T helper cells in the mucosa appear to mediate systemic T cell tolerance of dietary antigens. In the inflamed colon there is infiltration of the lamina propria by large numbers of monocytes which secrete interleukin-1, and the release of interferon-gamma appears to induce class II protein expression on colonic epithelial cells. Colonic epithelial cells from inflamed bowel may preferentially stimulate T helper cells so that local induction of class II MHC molecules on epithelial cells may amplify and localize secondary immune responses at the site of inflamed mucosa. Taken together, the aberrant expression of class II MHC molecules, breaches in epithelial cell integrity (resulting m exposure to luminal antigens including endotoxin and the increased numbers of monocytes found 10 inflamed mucosa suggest that the resulting distortions in antigen presentation contribute to the localization and persistence of the inflammatory lesion in inflammatory bowel disease.


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