02152nas a2200337 4500000000100000008004100001260000900042653002700051653002400078653002200102653001000124653002000134653003800154653001600192653001100208653001200219653002000231653002200251100001200273700001500285700001200300700001600312700001200328700001500340700001500355245015700370300001100527490000600538520125600544022001401800 1988 d c198810aAntibodies, Monoclonal10aAntigens, Bacterial10aAntigens, Surface10aBrain10aCross Reactions10aEnzyme-Linked Immunosorbent Assay10aGlycolipids10aHumans10aleprosy10aPolynucleotides10aRheumatoid Factor1 aZumla A1 aWilliams W1 aShall S1 aLocniskar M1 aLeigh I1 aMcAdam K P1 aIsenberg D00aHuman monoclonal antibodies to phenolic glycolipid-1 from leprosy patients cross react with poly(ADP-ribose), polynucleotides and tissue bound antigens. a183-950 v13 a

Antibodies which bind to poly(ADP-ribose) have been described in Systemic Lupus Erythematosus (SLE) and a variety of infectious diseases. Two IgM kappa human monoclonal antibodies (MAbs), TH3 and PR4, produced from the fusion of peripheral blood lymphocytes of leprosy patients with the GM4672 lymphoblastoid cell line, were found to bind to poly(ADP-ribose) in direct binding and inhibition ELISAs. Significant inhibition of binding of these MAbs to poly(ADP-ribose) occurred with phenolic glycolipid-1, the M. leprae specific glycolipid, ssDNA, dsDNA, poly(dT), as well as poly(ADP-ribose) itself. Up to 80% of binding of TH3, and 90% of binding of PR4, to poly(ADP-ribose) was inhibited by 10 mcg of ssDNA suggesting that there may be sharing of some conformational determinants. Although the serological binding profiles of TH3 and PR4 are similar, only PR4 was found to bind to basal keratinocytes of normal human interfollicular epidermis and astrocyte cytoplasm in normal brain tissue. These results support the concept that an antibody binding site may accommodate more than one epitope. Furthermore, small differences in antigen binding potential may distinguish relatively innocuous antibodies from those which may be more pathogenic.

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