HUMAN RHEUMATOID FACTOR CROSS-IDIOTYPES

三种人类单抗类风湿因子的发生 (MRF)多克隆间杂交独特型(XIds)Wa、PO和Bla 类风湿因子在各种疾病和免疫球蛋白中的作用 将使用鼠单抗对正常人进行研究 热不稳定构象重轻链的特性 XID抗原是由 定义MRF XIds的原始多克隆抗血清。 在B细胞谱系中出现的MRF XIds也将是 已访问。重链和轻链在氧化物形成中的作用 抗原和在确定MRF的抗原特异性方面 三组将由混合的重光决定 链重组。关于PO_xid的研究将会被说服 初步数据表明，这个XID决定因素，在 与WA和BLA XID相比，与 抗原结合部位。将特别重视学习 已被证明是高发的血乳酸xid 在类风湿关节炎的多克隆RFs中。RFS轴承 这种XID具有独特的特异性，因为它们与DNA反应- 组蛋白2A-2B为免疫球蛋白以外的抗原。氨基酸 轻链和重链可变区的序列 这一组的单克隆和多克隆RFs的原型将是 决心不仅是为了寻求对结构的洞察- 独特型-抗原特异性关系，但也限制了 可能存在于自身抗体的产生中。事件的发生 各种MRF互补决定区(CDR)抗原 关于多克隆类风湿因子、其他多克隆自身抗体 和正常的免疫球蛋白使用的抗血清提高到合成 CDR多肽将被确定以检验这一假设 某些CDR抗原选择性地与 自身抗体。

The occurrence of the three human monoclonal rheumatoid factor (mRF) cross idiotypes (XIds) WA, PO and BLA among polyclonal rheumatoid factors in various diseases and among immunogobulins in normals will be studied using mouse monoclonal antibodies with specifities for the heat labile conformational heavy-light chain XId antigens that are the main determinants recognized by the original polyclonal antisera which defined the mRF XIds. Occurrence of the mRF XIds in the B cell repertoire will also be accessed. The role of heavy and light chains in forming the XId antigens and in determining the antigen specificities of the mRFs of the three groups will be determined by assorted heavy-light chain recombinations. Studies on the PO XId will persue preliminary data which suggests that this XId determinant, in contrast to the WA and BLA XIds, is not associated with the antigen combining site. Special emphasis will be placed on study of the BLA XId which has been shown to occur in high incidence among polyclonal RFs in rheumatoid arthritis. The RFs bearing this XId have unique specificity in that they react with DNA- histone 2A-2B, antigen in addition to IgG. The amino acid sequence of the variable regions of the light and heavy chains of the prototype monoclonal and polyclonal RFs of this group will be determined in search of insights not only to the structural- idiotype-antigen specificity relationships but also restrictions that may be present in autoantibody production. The occurrence of various mRF complementary determining region (CDR) antigens on polyclonal rheumatoid factors, other polyclonal autoantibodies and normal immunoglobulins using antisera raised to synthetic CDR peptides will be determined to test the hypothesis that certain CDR antigens are selectively associated with autoantibodies.