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 Jaffee, Jonathan P Schneck, David H. Margulies, Andrew Mark 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
StatePublished - 2000

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Immunity
Ligands
T-Lymphocytes
Antigens
Peptides
Neoplasm Antigens
Epitopes
Cancer Vaccines
Amino Acid Substitution
Immunotherapy
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC-peptide-TCR complex. / Slansky, Jill E.; Rattis, Frédérique M.; Boyd, Lisa F.; Fahmy, Tarek; Jaffee, Elizabeth; Schneck, Jonathan P; Margulies, David H.; Pardoll, Andrew Mark.

In: Immunity, Vol. 13, No. 4, 2000, p. 529-538.

Research output: Contribution to journalArticle

Slansky, Jill E. ; Rattis, Frédérique M. ; Boyd, Lisa F. ; Fahmy, Tarek ; Jaffee, Elizabeth ; Schneck, Jonathan P ; Margulies, David H. ; Pardoll, Andrew Mark. / Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC-peptide-TCR complex. In: Immunity. 2000 ; Vol. 13, No. 4. pp. 529-538.
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