Molecular Basis of Regulatory Idiotopes

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Previous studies have led to the definition of a category of idiotope designated regulatory idiotopes which have been proposed to play an important role in idiotype-determined regulation of the immune response. High connectivity between B cell clones with various antigen specificities has been demonstrated, and such clones can be activated by antibodies specific for regulatory idiotopes. This phenomenon has been termed "cross-regulation". Furthermore, the majority of monoclonal antibodies expressing A48 regulatory idiotopes utilized V genes derived from the VH441-4 and VK10 families. Further studies will be aimed at exploiting these observations to gain further insight into the cellular and molecular mechanisms governing the expression of regulatory idiotopes. A rabbit antibody specific for a synthetic peptide corresponding to CDR1 of the heavy chain of A48 antibody and hybridomas from non- immunized mice selected with a VH441 germline gene probe have been prepared. The antibody to the synthetic peptide will be used to determine whether or not the antibodies sharing regulatory idiotopes express the same CDR1 sequence as the germline gene from which the A48 protein is derived. The antibodies produced by the hybridomas selected from non-immunized mice ("steady state") will be characterized with respect to their VH and VK families, their idiotypy, and their fine specificities. This should make it possible to determine the frequency of regulatory idiotopes in the steady state. The sequence of VH and VK genes encoding antibodies expressing regulatory idiotopes will be carried out and should enhance our understanding of the molecular factors contributing to the expression of regulatory idiotopes. The overall goal of these studies is to elucidate the immunochemical and molecular basis of regulatory iditopes. This knowledge should add to our understanding of the mechanisms by which immune responses are regulated.