Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Intestinal epithelial cells form a barrier separating gut lumen antigens from immune cells.
• These cells can express Human Leukocyte Antigen (HLA) class II molecules and act as antigen-presenting cells (APCs).
• CD4(+) T cells in the intestinal mucosa interact with APCs.

Purpose of the Study:

• To investigate how polarized intestinal epithelial cells process and present antigens via HLA class II molecules.
• To determine the role of antigen internalization surface (apical vs. basolateral) in this process.
• To assess the impact of the class II transactivator CIITA and inflammation on antigen presentation.

Main Methods:

• Utilized tetanus toxoid-specific and HLA-DR-restricted T lymphocytes.
• Engineered polarized intestinal epithelial cells to express HLA-DR molecules.
• Investigated antigen processing following apical or basolateral internalization.
• Co-expressed the class II transactivator CIITA.

Main Results:

• Intestinal epithelial cells require antigen internalization from the apical surface for HLA class II processing.
• CIITA expression enhances antigen processing from the basolateral surface without compromising barrier function.
• Peptide presentation to T cells via HLA class II molecules occurs exclusively at the basolateral surface.
• Antigen processing and presentation are polarized and influenced by inflammation.

Conclusions:

• Intestinal epithelial cells exhibit a polarized architecture for antigen processing and presentation.
• The functional outcome is dictated by the site of antigen entry and mucosal inflammation.
• This highlights a sophisticated mechanism for immune surveillance in the gut.