Enhanced Antigen-Specific Antitumor Immunity with Altered Peptide Ligands that Stabilize the MHC-Peptide-TCR Complex

T cell responsiveness to an epitope is affected both by its affinity for the presenting MHC molecule and the affinity of the MHC-peptide complex for TCR. One limitation of cancer immunotherapy is that natural tumor antigens elicit relatively weak T cell responses, in part because high-affinity T cel...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2000-10, Vol.13 (4), p.529-538
Main Authors: Slansky, Jill E, Rattis, Frédérique M, Boyd, Lisa F, Fahmy, Tarek, Jaffee, Elizabeth M, Schneck, Jonathan P, Margulies, David H, Pardoll, Drew M
Format: Article
Language:English
Subjects:
Alanine - metabolism
Amino Acid Substitution
Animals
Antigens, Neoplasm - immunology
Antigens, Neoplasm - metabolism
Clone Cells
Colorectal Neoplasms - immunology
Cytotoxicity, Immunologic - immunology
Epitopes, T-Lymphocyte - immunology
Epitopes, T-Lymphocyte - metabolism
Female
H-2 Antigens - metabolism
Histocompatibility Antigen H-2D
Ligands
Mice
Mice, Inbred BALB C
Oligopeptides - chemical synthesis
Oligopeptides - immunology
Oligopeptides - metabolism
Receptor-CD3 Complex, Antigen, T-Cell - metabolism
Surface Plasmon Resonance
T-Lymphocyte Subsets - immunology
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Summary:T cell responsiveness to an epitope is affected both by its affinity for the presenting MHC molecule and the affinity of the MHC-peptide complex for TCR. One limitation of cancer immunotherapy is that natural tumor antigens elicit relatively weak T cell responses, in part because high-affinity T cells are rendered tolerant to these antigens. We report here that amino acid substitutions in a natural MHC class I–restricted tumor antigen that increase the stability of the MHC-peptide-TCR complex are significantly more potent as tumor vaccines. The improved immunity results from enhanced in vivo expansion of T cells specific for the natural tumor epitope. These results indicate peptides that stabilize the MHC-peptide-TCR complex may provide superior antitumor immunity through enhanced stimulation of specific T cells.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)00052-2