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  • Title: Identification and selective destruction of shared epitopes in human chorionic gonadotropin beta subunit.
    Author: Jackson AM, Klonisch T, Lapthorn AJ, Berger P, Isaacs NW, Delves PJ, Lund T, Roitt IM.
    Journal: J Reprod Immunol; 1996 Aug; 31(1-2):21-36. PubMed ID: 8887120.
    Abstract:
    The feasibility of producing epitope-specific antigens by mutation of the gene is demonstrated, the aim being to eliminate unwanted surface epitopes yet allowing the natural folding of the protein to maintain the desired epitope(s). The model protein is the beta subunit of human chorionic gonadotropin (hCG beta) which previously has been used as an immunological contraceptive vaccine but has extensive cross-reaction with human luteinizing hormone. Of a series of mutants made, the mutant with substitutions of Glu for Arg 68, Ser for Arg 74, His for Gly 75 and His for Val 79, lost the ability to react with a panel of cross-reacting monoclonal antibodies while retaining the discontinuous and linear epitopes specific to the holo-hormone. In addition, allocation of amino acid residues to established epitope clusters could be made: residues 24, 25, 68 and 71 probably contribute to the cluster termed beta 3, residues 20, 21, 22, 75 and 77 to cluster beta 6 and residue 68 to clusters beta 2, beta 4 and beta 5.
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