Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells.
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.
Wang
Helen Y
HY
Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Peng
Guangyong
G
Guo
Zhong
Z
Shevach
Ethan M
EM
Wang
Rong-Fu
RF
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence; D018929:Cell Culture Techniques / Q000379:methods; D002461:Cell Line, Transformed; D002999:Clone Cells; D018076:DNA, Complementary / Q000302:isolation & purification; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006131:Growth Inhibitors / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D007376:Interleukin-2; D008024:Ligands; D010455:Peptides; C413657:adenocarcinoma antigen recognized by T cells-1