Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC-peptide-TCR complex

Jill E. Slansky, Frédérique M. Rattis, Lisa F. Boyd, Tarek Fahmy, Elizabeth M. Jaffee, Jonathan P. Schneck, David H. Margulies, Drew M. Pardoll

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)529-538
Number of pages10
JournalImmunity
Volume13
Issue number4
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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