Your browser version may not work well with NCBI's Web applications. More information here...
1: J Immunol. 2000 Oct 15;165(8):4264-71.
Related Articles, Links
Click here to read
Supra-agonist peptides enhance the reactivation of memory CTL responses.

Micheletti F, Canella A, Vertuani S, Marastoni M, Tosi L, Volinia S, Traniello S, Gavioli R.

Department of Biochemistry and Molecular Biology, Pharmaceutical Sciences, and Morphology and Embryology, University of Ferrara, Ferrara, Italy.

Single amino acid substitutions at TCR contacts may transform a natural peptide Ag in CTL ligands with partial agonist, antagonist, or null activity. We obtained peptide variants by changing nonanchor amino acid residues involved in MHC class I binding. These peptides were derived from a subdominant HLA-A2-presented, latent membrane protein 2-derived epitope expressed in EBV-infected cells and in EBV-associated tumors. We found that small structural changes produced ligands with vastly different activities. In particular, the variants that associated more stably to HLA-A2/molecules did not activate any CTL function, behaving as null ligands. Interestingly, T cell stimulations performed with the combination of null ligands and the natural epitope produced significantly higher specific CTL reactivation than reactivation of CTLs induced by the wild-type epitope alone. In addition, these particular variants activated memory CTL responses in the presence of concentrations of natural epitope that per se did not induce T cell responses. We show here that null ligands increased ZAP-70 tyrosine kinase activation induced by the natural epitope. Our results demonstrate for the first time that particular peptide variants, apparently behaving as null ligands, interact with the TCR, showing a supra-agonist activity. These variant peptides did not affect the effector T cell functions activated by the natural epitope. Supra-agonist peptides represent the counterpart of antagonists and may have important applications in the development of therapeutic peptides.

Publication Types:
PMID: 11035060 [PubMed - indexed for MEDLINE]