Adult guinea pigs were made unresponsive to a heterologous protein (e.g. bovine gamma globulin, or BGG) or a hapten-protein conjugate (e.g. p-aminobenzoic acid-bovine gamma globulin, or PABAγmiddot;BGG) by intraperitoneal injection of 80 mg cyclophosphamide and the specific antigen. This immunologic unresponsiveness developed to the specific antigen administered simultaneously with the cyclophosphamide, and not to any variants. Thus, animals unresponsive to PABAγmiddot;BGG remained unresponsive to the original antigen on challenge with a variant, but formed delayed hypersensitivity and circulating antibody to the variant. The specificity of immunologic unresponsiveness, therefore, seems more closely related to the whole antigen molecule than does delayed hypersensitivity.

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