E myeloma protein PS was digested with either papain or pepsin and fragments of the molecules were isolated. The papain digestion produced two fragments which correspond to Fc and Fab fragments of γG. Another fragment, Fc′, representing a portion of Fc was also obtained. The Fab fragments contained both γ chain determinants and ideotypic determinants, which are lacking in the Fc fragments. The γE class specific determinants are present in the Fc and multiple in specificity. Sedimentation coefficient of the Fc fragment was 5S and its molecular weight was estimated to be 94,000. After pepsin digestion of the E myeloma protein, approximately 75 per cent of the material was recovered as a 6S fragment. The fragment contained λ antigenic determinants, ideotypic determinants and a part of class specific determinants shared by Fc and Fc′, and corresponded to F(ab′)2. Among these fragments, only the Fc fragments blocked passive sensitization of the primate skin with reaginic antibody. The fragments passively sensitized human leukocytes and monkey lung. The sensitized leukocytes released histamine by anti-γE and sensitized moneky lung released both histamine and slow reacting substance of anaphylaxis (SRS-A) by the antibody. These results showed that the Fc fragments combined with the cells and tissues upon passive sensitization. The Fc and F(ab′)2 fragments were aggregated by coupling with bisdiazotized benzidine. Nonspecifically aggregated Fc fragments gave erythema-wheal reactions in normal human and monkey skin, whereas monomer Fc did not. The aggregated Fc but not monomer Fc released histamine from normal human leukocytes and both histamine and SRS-A from monkey lung. Neither the aggregated nor the non-aggregated F(ab′)2 induced skin reaction or released the chemical mediators. The results suggested that structural changes in the Fc portion of γE molecules initiate enzymatic sequences leading to the release of the chemical mediators.
ASJC Scopus subject areas
- General Medicine