Joint-derived T cells in rheumatoid arthritis react with self-immunoglobulin heavy chains or immunoglobulin-binding proteins that copurify with immunoglobulin.
Rheumatoid arthritis patients were found to have CD4+ T cells that proliferate in response to autologous synovial fluid and plasma. T cell clones and polyclonal T cell lines were found to respond to antigen(s) eluted from protein A Sepharose and anti-human immunoglobulin (Ig) antibody Sepharose. The antigen(s) was further resolved to fractions that contained intact Ig or Ig heavy chain since the T cells responded to > 100 kDa and 40-60 kDa polypeptides derived from purified Ig under nonreducing and reducing conditions, respectively. These results indicated that the antigen(s) is either Ig heavy chain or Ig-binding proteins that copurify with Ig and Ig subunits. Pepsin and papain digestion of the antigenic fractions eluted from protein A destroyed the T cell reactivity. Since most Fab regions are resistant to these enzymes, further analyses are required to localize the antigenic epitope(s). The presence of Ig- or Ig-antigen complex-reactive T cells in arthritic joints implies that B cells expressing anti-Ig antibody (i.e. rheumatoid factor) may play an important role in antigen presentation to autoreactive T cells.
ImmuLogic Pharmaceutical Corporation, Palo Alto, CA 94304.
W C
WC
van Schooten
D
D
Devereux
C H
CH
Ho
J
J
Quan
B A
BA
Aguilar
C J
CJ
Rust
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D017951:Antigen Presentation / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007719:Knee Joint / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012685:Sepharose / Q000031:analogs & derivatives; D013582:Synovial Fluid / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013205:Staphylococcal Protein A
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D002352:Carrier Proteins; D006684:HLA-DR Antigens; D007143:Immunoglobulin Heavy Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012685:Sepharose; C042030:Staphylococcal protein A-sepharose; D013205:Staphylococcal Protein A