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Polarized expression of CD74 by gastric epithelial cells
Carlos A Barrera1, Ellen J Beswick, Johanna C Sierra
1Department of Pediatrics, University of Texas Medical Branch, Galveston, USA.
Insights
Gastric epithelial cells (GEC) constitutively express invariant chain (Ii), a protein crucial for major histocompatibility complex (MHC) class II function. This finding reveals a novel role for GEC in local immune responses, particularly during Helicobacter pylori infection.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- Invariant chain (Ii) is essential for major histocompatibility complex (MHC) class II molecule function.
- MHC class II and Ii expression were traditionally limited to antigen-presenting cells (APCs).
- Inflammation can induce MHC class II expression in non-classical APCs like mucosal epithelial cells.
Purpose of the Study:
- To investigate invariant chain (Ii) expression in gastric epithelial cells (GEC).
- To determine if GEC-expressed MHC class II molecules are regulated by Ii.
- To support the role of GEC in local immune and inflammatory responses during Helicobacter pylori infection.
Main Methods:
- Examined Ii expression on GEC from human biopsy samples.
- Confirmed Ii expression using independent methods on GEC lines.
- Detected Ii mRNA via RT-PCR and analyzed protein isoforms.
Main Results:
- Demonstrated constitutive expression of invariant chain (Ii) by human GEC.
- Observed high-level surface expression of Ii on GEC.
- Found Ii expression to be polarized to the apical surface of GEC.
Conclusions:
- Human GEC constitutively express invariant chain (Ii).
- This suggests Ii regulates MHC class II function in GEC.
- Highlights a potential role for GEC in local immune responses, especially in H. pylori infection.
Abstract:
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.
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