It is intended to provide a novel preventive/remedy for diseases with immune abnormality which can effectively act as a super-antigen without being neutralized by a neutralizing antibody to Staphylococcus enterotoxin B (SEB) known as a super-antigen. Namely, an SEB modification having a lowered reactivity with a neutralizing antibody to SEB (anti-SEB antibody) and a preventive/remedy for diseases with immune abnormality which contains this modification as the active ingredient. This SEB modification can be obtained via amino acid substitution in the amino acid sequence of SEB, in particular the amino acid sequence at the epitope part recognized by the anti-SEB antibody by using evolutionary molecular engineering techniques.