Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells

Helen Yicheng Wang, Guangyong Peng, Zhong Guo, Ethan M. Shevach, Rongfu Wang

Research output: Contribution to journalArticle

139 Scopus citations

Abstract

CD4+ regulatory T (Treg) cells play an important role in the maintenance of immunological self-tolerance by suppressing immune responses against autoimmune diseases and cancer. Yet very little is known about the natural antigenic ligands that preferentially activate CD4+ Treg cells. Here we report the establishment of tumor-specific CD4+ Treg cell clones from tumor-infiltrating lymphocytes (TILs) of cancer patients, and the identification of an Ag recognized by Treg cells (ARTC1) gene encoding a peptide ligand recognized by tumor-specific TIL164 CD4+ Treg cells. The mutations in a gene encoding an ARTC1 in 164mel tumor cells resulted in the translation of a gene product containing the peptide ligand recognized by CD4+ Treg cells. ARTC1 peptide-activated CD4+ Treg cells suppress the physiological function (proliferation and IL-2 secretion) of melanoma-reactive T cells. Furthermore, 164mel tumor cells, but not tumor lysates pulsed on B cells, were capable of activating TIL164 CD4+ Treg cells. These results suggest that tumor cells may uniquely present an array of peptide ligands that preferentially recruit and activate CD4+ Treg cells in sites where tumor-specific self-peptide is expressed, leading to the induction of local and tumor-specific immune suppression.

Original languageEnglish (US)
Pages (from-to)2661-2670
Number of pages10
JournalJournal of Immunology
Volume174
Issue number5
DOIs
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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