The research objectives are: (1) to obtain more information on the structure of immunoglobulins and on the nature of somatic variations that operate on germline genes. For antibodies of an idiotypic family, attempts will be made to correlate sequences with the 3-D structure of one or more members of the family; (2) to better define and quantify antiidiotypes that express an internal image of the original antigen, and to use the principle for induction of antiviral antibodies; (3) to study sequence variations among IgE antibodies of defined idiotype and to compare the nature and extent of these variations with those occurring in other classes; (4) to initiate studies on the regulation of IgE. Project 1 will be approached through X-ray crystallography, carried out by Dr. R. Poljak on monoclonal antibodies we are supplying, and by determination of amino acid sequences (inferred from mRNA sequences). The sequences of minor idiotypes, that are closely related to but divergent from a major cross-reactive idiotype, should add a dimension to the degree of variation on germline DNA sequences that can be investigated. We will quantify anti-Id expressing an internal image of the antigen in several systems and attempt to induce antiviral antibodies (possibly protective) against pseudorabies virus and cytomegalovirus. IgE monoclonal antibodies that express major and minor idiotypes will be sequenced to ascertain the patterns of variability in this Ig class. Finally, sensitive quantitative techniques for total and idiotype-bearing IgE antiphenylarsonate antibodies will be used to initiate studies of IgE regulation. These studies should add to our knowledge of mechanisms of antibody biosynthesis and regulation. Information on structural variations in antibodies is relevant to our understanding of antibody biosynthesis. Studies on internal images of antigens in certain antiidiotypic antibodies may lead to the use of such antibodies as vaccines or as modulators of physiological processes involving cell surface receptors. Studies of IgE and its regulation are relevant to the control of reactions of immediate hypersensitivity, including allergies.
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