IgM Antibodies Can Access Cryptic Antigens Denied to IgG: Hypothesis on Novel Binding Mechanism

IgM Antibodies Can Access Cryptic Antigens Denied to IgG: Hypothesis on Novel Binding Mechanism

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Antibodies are well-known protein mediators of immunity.IgM is the primordial member and the neglected sibling of the later-evolved and more proficient IgG in regard to their therapeutic and diagnostic use.Serendipitously, however, we found a paradox: While murine IgM antibodies specific for guanosine triphosphate (GTP) were able to recognize animationbengal.com native guanylyl antigens found in primate or rat muscle tissues by immunofluorescence assays (which mimicked the auto-antibodies from autoimmune patients to skeletal or smooth muscle), the murine and human IgG counterparts failed.The results were replicated in cell-free direct binding assays using small latex microspheres decorated densely with GTP.

The IgG antibodies could bind, however, if GTP was presented more spaciously on larger particles or as a univalent hapten.Accordingly, oligomerization of GTP (30-mer) destroyed the binding of the IgG antibodies but enhanced that of the IgMs in inhibition ELISA.We reason that, contrary to current belief, IgM does not bind in a lock-and-key manner like IgG.We hypothesize that whereas the intact and rigid antigen-binding site of IgG hinders the antibody from docking with antigens that are obstructed, in IgM, the two component polypeptides of the antigen-binding site can dissociate from each other and navigate individually through obstacles like the ancestral single-polypeptide antibodies found in sharks and camelids, both components eventually re-grouping around the antigen.

We g35 coupe fender further speculate that polyreactive IgMs, which enigmatically bind to more than one type of antigen, use the same modus operandi.These findings call for a re-look at the clinical potential of IgM antibodies particularly in specific areas of cancer therapy, tissue pathology and vaccine design, where IgG antibodies have failed due to target inaccessibility.