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HLA-Derived Peptides as Novel Immunomodulatory Therapeutics

BARBARA MURPHY^* and ALAN M. KRENSKY

^* Department of Medicine, Mount Sinai School of Medicine, New York, New York
Department of Pediatrics, Stanford University School of Medicine, Stanford, California.

Correspondence to Dr. Alan M. Krensky, Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5208. Phone: 650-498-6073; Fax: 650-498-6077; E-mail: mn.aln{at}forsythe.stanford.edu

Abstract

Abstract. A growing body of experimental evidence demonstrates that synthetic peptides corresponding to linear sequences of MHC (HLA in humans) proteins have immunomodulatory effects in vitro and in vivo in animal models and in humans. Although the original concept was that these peptides inhibited antigen recognition at the MHC-T cell receptor interface via physical blockade, it is now clear that the mechanisms responsible for the myriad of functional effects are more complex. Recent findings show that some peptides affect signal transduction and cell cycle progression. Fragments of MHC molecules can dampen or downregulate immune responses via a variety of mechanisms. Some soluble MHC molecules or synthetic peptides are capable of inducing and maintaining immunologic tolerance in animals. This information suggests that synthetic peptides themselves or drugs mimicking their effects may represent a new class of immunotherapeutics.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673