The research protocol is directed toward elucidation of those structure-function relationships of the active site of selected monoclonal human autoantibodies which are responsible for mediating antibody specificity. By obtaining these experimental data, information will be gained which may clarify a) the mechanisms of autoantibody formation in general and b) the means by which variations in specificity and binding-site avidity occur. These data will be obtained by isolation of monoclonal anti-IgG human autoantibodies (rheumatoid factors), determination of their precise antigenic specificity, antibody site binding avidity, and correlation of these with the primary amino acid structure to be determined for their active antibody sites. These autoantibodies will then be utilized as examples of "normally structured" immunoglobulins and will be compared to a select group of myeloma proteins which exhibit evidences of deranged primary structure. Comparisons between the normal and abnormal immunoglobulins will be made utilizing the parameters of molecular weight, sedimentation value, disulphide bond number, and susceptibility to papain enzymatic digestion. Specifically, evidences for genetic deletions of primary structure in the myeloma proteins will be sought. This information, if obtained, may point to a pathogenetic lesion in the plasma cell which produces the myeloma protein.