NIH/3T3 Fibroblasts Selectively Activate T Cells Specific for Posttranslationally Modified Collagen Type II

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Synovial fibroblasts (SF) are implicated in rheumatoid arthritis (RA) pathogenesis, potentially by presenting antigens.
• Fibroblasts can express MHC class II (MHCII) molecules, enabling antigen presentation to immune cells.

Purpose of the Study:

• To investigate if various fibroblast types can process and present type II collagen (COL2), an RA autoantigen.
• To determine the role of NIH/3T3 fibroblasts in initiating RA pathogenesis and T-cell activation.

Main Methods:

• Utilized MHCII/Aq-restricted T-cell hybridoma lines specific for a COL2 epitope (COL2259-273).
• Assessed activation of T-cell clones by synovial, dermal, thymic, LS48, and NIH/3T3 fibroblasts.
• Investigated antigen-independent activation mechanisms involving T-cell receptor (TCR) complex.

Main Results:

• NIH/3T3 fibroblasts activated T-cell clones recognizing posttranslationally modified COL2259-273.
• NIH/3T3 cells, unlike other fibroblasts, stimulated a hybridoma specific for glycosylated COL2259-273 (Gal264).
• NIH/3T3 fibroblasts activated COL2-specific T-cell hybridomas without exogenous COL2 or modified peptide, via a contact-dependent TCR mechanism.

Conclusions:

• NIH/3T3 fibroblasts possess a unique capacity to activate specific T-cell hybridomas, independent of antigen presence.
• This antigen-independent activation mechanism may contribute to rheumatoid arthritis initiation.
• Fibroblast-TCR interactions represent a potential pathway in autoimmune disease pathogenesis.