Shared V-region antigens and cross-reacting specificities of human IgG anti-F(ab')2 and anti-DNA antibodies.

Affinity-isolated IgG anti-F(ab')2 (APAF) and anti-DNA (APAD) from normal subjects as well as patients with systemic lupus erythematosus (SLE) were studied for overlapping antibody specificities as well as shared V-region antigens using rabbit antisera prepared against F(ab')2 fragments of SLE IgG APAD or IgG APAF from normal individuals. When absorbed free of antibody reacting with normal human IgG, both types of rabbit anti-Ids showed cross-reacting antigenic determinants shared by APAF and APAD from both normals and SLE patients. Immunodepletion of APAD or APAF IgG fractions using immunoabsorbents composed of such rabbit anti-SLE F(ab')2 APAD or anti-normal IgG APAF antibodies produced substantial decrements (40-90%) in ELISA anti-F(ab')2, antiSm, anti-Sm/RNP, and anti-DNA reactivity. Parallel decrements in human anti-DNA Id markers F4 and 3I were also recorded after immunoadsorbent depletions of SLE APADs. Absorption of rabbit IgG anti-SLE APAD F(ab')2 antibody with DNA-Sepharose produced a relative increment in ELISA anti-DNA reactivity but a marked parallel decrement in reactivity for the original SLE APAD immunogen. Eluates from DNA-Sepharose contained rabbit epibody showing moderate anti-DNA affinity and high-affinity anti-APAD idiotypic activity. This epibody fraction showed relative concentration of rabbit IgG antibodies capable of blocking combining sites of SLE IgG APAD reacting with DNA on the ELISA plate. Our findings indicate a previously unexpected close antigenic and specificity overlap between human IgG anti-F(ab')2 and anti-DNA antibodies. Moreover, they emphasize a surprising relative infrequency of anti-DNA idiotypic antibodies capable of blocking combining sites in animals immunized with SLE F(ab')2 APAD. This finding may relate to an intrinsic defect of anti-Id regulation in SLE.