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2001 | 49 | 4 | 271-278
Article title

Enhancing cytotoxic t cell responses with altered-peptide ligands

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EN
Abstracts
EN
Interest in class I MHC-mediated immunotherapy is growing rapidly. In order to fight a virus or cancer effectively, a successful immunotherapeutic must activate a large number of specific CD8+ T cells and also generate immunological memory. Attempts to generate immune responses towards tumor- or virus-derived peptides have frequently been frustrated by the nature of the peptide antigen itself. Either the peptide does not bind well to its cognate MHC, or the T cells directed towards it have been functionally inactivated in vivo. Altered-peptide ligands are an effective way to circumvent these problems. However, generating enhanced binding of altered peptides to class I MHC while still maintaining recognition of the wild-type peptide is not straightforward. Many groups design enhanced binding peptides by substituting the observed anchor residues with those that are most preferred by the class I MHC molecule. For many antigenic peptides, this approach does not work. Furthermore, if a higher affinity peptide is designed, the substitutions may result in reduced recognition by CD8+ T cells. Therefore, the design of an altered-peptide ligand requires careful testing of each candidate therapeutic in terms of affinity for class I MHC and immunological reactivity. Lastly, immunotherapy using class I MHC must also take into account the large genetic heterogeneity in the population. A therapeutic that is only effective for 5-10 percent of the population is not as attractive as one that works for over 90% of the population. The use of MHC supertypes (groups of class I MHC allotypes that share similar peptide-binding characteristics) shows great promise in overcoming this problem.
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Year
Volume
49
Issue
4
Pages
271-278
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Contributors
author
author
References
Document Type
REVIEW
Publication order reference
R. Zhao, Department of Microbiology and Immunology, and Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
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bwmeta1.element.element-from-psjc-b34a0e80-46c2-362e-a86d-89d02be72a6f
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