Human vascular endothelial cells process and present autoantigen to human T cell lines

Area of Science:

• Immunology
• Cell Biology

Background:

• Myasthenia gravis (MG) involves T cell responses to acetylcholine receptor (AChR) epitopes.
• Endothelial cells can act as antigen-presenting cells, but their role in T cell activation requires further investigation.

Purpose of the Study:

• To evaluate the effectiveness of human umbilical vein endothelial cells (HUVECs) as accessory cells for T cell activation in myasthenia gravis.
• To compare the antigen-presenting capabilities of HUVECs with peripheral blood-derived antigen-presenting cells.

Main Methods:

• T cell clones and lines from MG patients specific for AChR alpha subunit epitopes were used.
• HUVECs were induced with interferon-gamma (IFN-γ) to express HLA-DR and HLA-DQ.
• Antigen presentation assays were performed using specific peptides and full-length recombinant AChR alpha subunit (r1-437).
• Chloroquine inhibition and monoclonal antibody (mAb) blocking studies were employed to assess presentation pathways and accessory signaling.

Main Results:

• Induced HUVECs efficiently presented AChR alpha subunit peptides to HLA-DR- and HLA-DQw5-restricted T cell lines.
• HUVECs processed full-length r1-437 for both T cell lines, with presentation sensitive to chloroquine.
• Endothelial cell presentation was 1.5- to 3.0-fold less efficient than peripheral blood cells.
• Accessory signaling differed, with peripheral blood cells utilizing CD28 ligands and HUVECs using LFA-3.

Conclusions:

• Cultured HUVECs can function as accessory cells for T cell activation by presenting AChR epitopes relevant to myasthenia gravis.
• Differences in accessory signaling molecules (CD28 vs. LFA-3) may contribute to the observed variations in presentation efficiency.
• HUVECs represent a valuable model for studying T cell-autoantigen interactions in autoimmune diseases.