Brief Definitive Report C1 FIXATION AND CLASSICAL COMPLEMENT PATHWAY ACTIVATION BY A FRAGMENT OF THE Cj14 DOMAIN OF IgM*

An insight into the structural features of human Waldenstr6m IgM proteins which are responsible for their capacity to bind and activate the first component of complement (C) has been obtained . The basic approach has involved enzymatic and chemical fragmentation of the IgM molecule followed by examination of the resulting fragments for C-fixing activity . A 6,800 mol wt fragment obtained from the terminal C/,4 domain of a Waldenstr6m IgM molecule has been shown to bind active C1 (C1) (1). This subfragment of IgM, which was designated the C,,4 fragment, was found to be composed of the CHc4 domain of the Fcp, minus two tryptic peptides in the center of the loop . The first set of experiments described in this communication were designed to evaluate the dependence of C1-binding ability upon the presence of the intrachain disulfide bond in the C,,4 fragment . In addition, the CH4 fragment before and after reduction, as well as each of its component chains, were examined for their ability to trigger the activation of the classical C pathway. Based upon these studies we are able to present evidence suggesting that the C1-activating function remains intact in these three fragments.