Ermel R, Kenny T, Benisek W, Roberts M, Robbins D
Department of Internal Medicine, School of Medicine, University of California, Davis 95616.
Clin Immunol Immunopathol. 1992 Jun;63(3):259-66. doi: 10.1016/0090-1229(92)90231-c.
The immunopathologic process of rheumatoid arthritis (RA) is primarily expressed in the synovium where rheumatoid factor (RF) synthesis is concentrated. We hypothesized that RF synthesized by rheumatoid synovial cells (RSC) may be driven via a T cell-mediated immune response developed against IgG3 epitopes. To identify and characterize specific RSC RF epitopes and T cell antigens, two 28 amino acid peptides homologous with the C-terminus of IgG1 (P1) and IgG3 [G3m(5)] (P3) were synthesized and used in RF-binding studies and lymphocyte proliferation assays. Our results indicate that (i) the C-terminus of the CH3 domain contains epitopes for IgG3-reactive RSC RF; (ii) IgG3-reactive RSC RF binds primarily to IgG3 [G3m(5)]; (iii) P3 stimulated proliferation of T lymphocytes from both RA peripheral blood and RSC; and (iv) RF production was enhanced by P3 in selected RA cell cultures. These observations suggest that the C-terminus of IgG3 allotype G3m(5) may be important in T cell activation and RF production in RA.
类风湿关节炎（RA）的免疫病理过程主要表现在滑膜中，类风湿因子（RF）的合成集中于此。我们推测，类风湿滑膜细胞（RSC）合成的RF可能是通过针对IgG3表位产生的T细胞介导的免疫反应驱动的。为了鉴定和表征特定的RSC RF表位和T细胞抗原，合成了两条与IgG1（P1）和IgG3 [G3m(5)]（P3）的C末端同源的28个氨基酸的肽，并用于RF结合研究和淋巴细胞增殖试验。我们的结果表明：（i）CH3结构域的C末端含有IgG3反应性RSC RF的表位；（ii）IgG3反应性RSC RF主要与IgG3 [G3m(5)]结合；（iii）P3刺激来自RA外周血和RSC的T淋巴细胞增殖；（iv）在选定的RA细胞培养物中，P3增强了RF的产生。这些观察结果表明，IgG3同种异型G3m(5)的C末端可能在RA的T细胞活化和RF产生中起重要作用。
