HUMAN RHEUMATOID FACTOR CROSS-IDIOTYPES

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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.