Pc. Swanson et al., LIGAND RECOGNITION BY ANTI-DNA AUTOANTIBODIES - AFFINITY, SPECIFICITY, AND MODE OF BINDING, Biochemistry, 35(5), 1996, pp. 1624-1633
Understanding the molecular basis of DNA recognition by anti-DNA autoa
ntibodies is a key element in defining the role of antibody . DNA comp
lexes in the pathogenesis of the autoimmune disorder systemic lupus er
ythematosus. As part of our efforts to relate anti-DNA affinity and sp
ecificity to antibody structure, and ultimately to disease pathogenesi
s, we have generated a panel of eight anti-DNA mAbs from an autoimmune
MRL MpJ-lpr/lpr mouse and have assessed the binding properties of the
se antibodies. We find that none of our anti-DNA mAbs bind to RNA and
only one low-affinity mAb cross-reacts with non-DNA antigens, albeit w
eakly. None of the mAbs in our panel bind double-stranded DNA exclusiv
ely. Antibodies that recognize single-stranded DNA can be categorized
into two groups based on their affinity and apparent mode of binding.
One group possesses relatively high affinity for oligo(dT) and may rec
ognize single-stranded DNA ligands by accommodating thymine bases in h
ydrophobic pockets on the antigen binding site. The second group binds
more weakly, apparently recognizes single-stranded DNA nonspecificall
y, and in some cases also binds double-stranded DNA. Although differen
t mechanisms are used for binding single- and double-stranded ligands,
the mode of DNA recognition appears conserved within groups of antibo
dies.