Immunoinhibitory DNA vaccine protects against autoimmune diabetes through cDNA encoding a selective CTLA-4 (CD152) ligand.

作者: Gerald J. Prud'homme , Yigang Chang , Xiaoying Li

DOI: 10.1089/10430340252792521

关键词:

摘要: Cytotoxic T lymphocyte antigen 4 (CTLA-4 or CD152) is a strong negative regulator of cell activity. Like CD28 (a positive regulator) it binds to B7-1 and B7-2, there no known natural selective ligand. Monoclonal antibodies CTLA-4 generally have masking effect, enhancing rather than suppressing responses. However, single amino acid substitution in (W88 > A; denoted B7-1wa) abrogates binding but not CTLA-4. We constructed plasmids encoding B7-1wa, as cell-surface Ig fusion proteins. In bound state, B7-1-Ig enhanced CD3-mediated activation, B7-1wa-Ig was inhibitory, expected To alter immunity vivo, we inoculated mice intramuscularly (i.m.) with carcinoembryonic (CEA) plasmid. Gene transfer amplified by electroporation. Co-injection B7-1wa (membrane-bound form) plasmid blocked induction anti-CEA immunity, whereas stimulatory. studied this DNA covaccination method nonobese diabetic (...

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