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

J Immunol. 2005 Mar 1;174(5):2661-70. doi: 10.4049/jimmunol.174.5.2661.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation* / genetics
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / isolation & purification
  • Antigens, Neoplasm / metabolism*
  • Base Sequence
  • Cell Culture Techniques / methods
  • Cell Line, Transformed
  • Clone Cells
  • DNA, Complementary / isolation & purification
  • Epitopes, T-Lymphocyte / immunology*
  • Growth Inhibitors / genetics
  • Growth Inhibitors / immunology
  • Growth Inhibitors / isolation & purification
  • Growth Inhibitors / metabolism
  • Humans
  • Immunophenotyping
  • Interleukin-2 / antagonists & inhibitors
  • Interleukin-2 / metabolism
  • Ligands
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Melanoma / immunology
  • Melanoma / metabolism
  • Melanoma / pathology
  • Molecular Sequence Data
  • Mutation
  • Peptides / genetics
  • Peptides / immunology
  • Peptides / isolation & purification
  • Peptides / metabolism*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • DNA, Complementary
  • Epitopes, T-Lymphocyte
  • Growth Inhibitors
  • Interleukin-2
  • Ligands
  • Peptides
  • adenocarcinoma antigen recognized by T cells-1

Associated data

  • GENBANK/AY527413