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Degradation of Human IgM Anti-γ-Globulin by Pepsin provides Evidence of an Active Fragment


RABBIT antibodies of the immunoglobulin G (IgG) class have been shown to be cleaved by pepsin, in the absence of mercaptans, into bivalent fragments1. These fragments, termed F(ab′)2-fragments, sediment in the ultracentrifuge at 5S and are resistant to further cleavage. Similar products have been observed after peptic digestion of human IgG antibodies2. In contrast, others found that human immunoglobulin M (IgM) was rapidly degraded by pepsin into a heterogeneous mixture of small fragments3–5. Incubation of IgM cold agglutinins with the enzyme in buffer at pH. 4.0 and 37° C for 30 min, or 4° C for 48 h, resulted in the complete loss of red cell agglutinating activity3. Efforts to demonstrate residual combining activity by an indirect agglutination technique were unsuccessful. Similarly, treatment of IgM anti-γ-globulins (rheumatoid factors) by pepsin at 4° C for 48 h resulted essentially in complete loss of activity, as measured by several agglutination methods3. I have examined further the degradation of human IgM anti-γ-globulins by pepsin and present evidence of the production of fragments that retain the capacity to combine with human IgG.

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SCHROHENLOHER, R. Degradation of Human IgM Anti-γ-Globulin by Pepsin provides Evidence of an Active Fragment. Nature 223, 308–310 (1969).

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