Polyreactivity of natural antibodies: exchange by HL-fragments.
The polyreactivity of binding (formation of antibody (AB) complexes not only with specific but also with foreign antigens) is a widespread phenomenon that in some cases can be caused by a conformational lability of the antigen-binding sites of antibodies (which increases upon treatment with various destabilizing agents) and leads to AB binding with very different antigens. Some ABs exist as dimers of the initial ABs and their idiotypes (or anti-idiotypes) capable of producing intramolecular cyclic complexes with features of polyreactants. Another mechanism of binding polyreactivity is an exchange in blood by halves of IgG4 molecules (HL-fragments) against various antigens. Also, for the first time catalytic polyfunctionality of human milk ABs has been detected, which is caused by an exchange by HL-fragments between molecules of λ- and κ-IgG (IgG1-IgG4) and also by λ- and κ-sIgA against different antigens with formation of very different chimeric antibodies. This review considers all possible pathways of formation of polyspecific immunoglobulins and their biological functions described in the literature, as well as mechanisms of binding polyreactivity and catalytic polyfunctionality of natural antibodies.
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, 630090, Russia. nevinsky@niboch.nsc.ru.
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Sedykh
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Buneva
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Nevinsky
D000906:Antibodies / Q000737:chemistry / Q000378:metabolism*; D017151:Antibodies, Catalytic / Q000737:chemistry / Q000378:metabolism; D022801:Complementarity Determining Regions; D019281:Dimerization; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000378:metabolism*; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000378:metabolism*; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism*; D008895:Milk, Human / Q000378:metabolism
D000906:Antibodies; D017151:Antibodies, Catalytic; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins