STUDIES ON STRUCTURAL AND BIOLOGICAL FUNCTIONS OF C-MU-3 AND C-MU-4 DOMAINS OF IGM

  • 1 January 1978
    • journal article
    • research article
    • Vol. 34  (3) , 449-458
Abstract
The development of methods for the production of intact C.mu.3 [.mu.3 constant region] and C.mu.4 domains of Ig[immunoglobulin]M made possible the assessment of some of their structural and biological functions. Antiserum against Fc.mu. fragment detected both domains and illustrated their complete antigenic non-identity. Circular dichroism spectroscopy and the retention of antigenicity indicated that both domains had retained most of their native structure. No interaction of the type C.mu.3-C.mu.3, C.mu.4-C.mu.4 or C.mu.3-C.mu.4 could be detected under non-dissociating conditions by analytical ultracentrifugation or molecular exclusion chromatography experiments. The transmission of effector messages between the Fab and Fc parts of IgM apparently takes place through structural changes at the quaternary level. C.hivin.1[activated complement component 1]-fixation experiments with IgM and several of its fragments and domains demonstrated the following results: the C.mu.4 domain contains the C.hivin.1-fixing site; the high C.hivin.1-fixing capacity of IgM or Fc5.mu. cannot be explained on the basis of a simple accumulative model of complement fixing domains; the C.hivin.1-fixing site is independent of the native structure of the C.mu.4 domain; and the C.hivin.1-fixing site does not contain carbohydrate. Examination of the IgM receptor on the surface of human T lymphocytes gave the following conclusions: C.mu.4 domain is primarily responsible for the reaction and C.mu.3 domain has very little affinity; native structure is essential for the reaction because reduction and alkylation of the C.mu.4 domain destroyed both its original conformation and affinity for this receptor; IgM and Fc5.mu. had a much greater affinity for the receptor than monomeric subunits; and carbohydrate on C.mu.4 domain is not involved in the affinity reaction.