Cathepsin G is differentially expressed in primary human antigen-presenting cells

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Cathepsins are crucial for antigen processing and presentation via MHC class II molecules to CD4(+) T cells.
• Antigen processing differs between monocyte-derived dendritic cells (DCs) and primary human DCs.
• Human myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) exhibit distinct cathepsin profiles.

Purpose of the Study:

• To investigate the differential distribution of cathepsins in human mDC and pDC subsets.
• To determine the role of serine protease cathepsin G (CatG) in the processing and presentation of the Multiple Sclerosis-associated autoantigen myelin basic protein (MBP).

Main Methods:

• Detection of cathepsin G (CatG) in human mDC and pDC subsets.
• Utilizing a non-CatG expressing fibroblast cell line and fibroblasts preloaded with purified CatG.
• Assessing T cell proliferation in response to MBP antigen presented by CatG-loaded fibroblasts.

Main Results:

• Cathepsin G (CatG) was detected in mDC1, mDC2, pDC, and cortical thymic epithelial cells (cTEC), with high levels in pDC.
• Preloading fibroblasts with CatG led to a significant decrease in MBP84-98-specific T cell proliferation compared to control cells.
• This suggests CatG influences antigen processing and presentation.

Conclusions:

• Primary human antigen-presenting cells display unique cathepsin processing signatures.
• Cathepsin G (CatG) plays a potentially significant functional role in antigen presentation, impacting T cell responses.