Abstract |
Many CTL epitopes of clinical importance, particularly those derived from tumor Ags, display relatively poor MHC binding affinity and stability. Because in vivo immunogenicity, and thus the efficacy of peptide-based vaccines, is thought to be determined by MHC/ peptide complex stability, there is a need to develop a simple strategy for enhancing the binding of suboptimal epitopes. Toward this goal, the ability to enhance suboptimal peptides through covalent linkage to beta2-microglobulin (beta2m) was explored. Two suboptimal variants of a high-affinity Db-restricted influenza nucleoprotein peptide were covalently linked, via a polypeptide spacer, to the amino terminus of human beta2m and the recombinant fusion proteins expressed in Escherichia coli. When compared with their uncoupled counterparts, the beta2m-linked epitopes display enhanced MHC stabilization and antigenicity. Thus, tethering epitopes to beta2m provides a simple method for augmenting the biological activity of suboptimal peptides and could be useful in the design of peptide-based vaccines or immunotherapeutics.
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Authors | R A Uger, S M Chan, B H Barber |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 162
Issue 10
Pg. 6024-8
(May 15 1999)
ISSN: 0022-1767 [Print] United States |
PMID | 10229842
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Viral
- Epitopes
- Nucleoproteins
- Recombinant Fusion Proteins
- Vaccines, Synthetic
- Viral Core Proteins
- beta 2-Microglobulin
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Topics |
- Animals
- Antigens, Viral
(immunology)
- Cytotoxicity, Immunologic
- Drug Design
- Epitopes
(genetics, immunology)
- Humans
- Major Histocompatibility Complex
(immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Nucleoproteins
(genetics, immunology)
- Orthomyxoviridae
(genetics, immunology)
- Protein Binding
- Recombinant Fusion Proteins
(immunology)
- T-Lymphocytes, Cytotoxic
(immunology)
- Vaccines, Synthetic
- Viral Core Proteins
(genetics, immunology)
- beta 2-Microglobulin
(genetics, immunology)
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