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

Immunity. 2000 Oct;13(4):529-38. doi: 10.1016/s1074-7613(00)00052-2.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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


  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Ligands
  • Oligopeptides
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Alanine