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Recognition of a New ARTC1 Peptide Ligand Uniquely Expressed in Tumor Cells by Antigen-Specific CD4⁺ Regulatory T Cells¹

Helen Y. Wang^*, Guangyong Peng^*, Zhong Guo^*, Ethan M. Shevach and Rong-Fu Wang^2,*

^* Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, Houston, TX 77030; and Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

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.

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The JI 2005 174: 2447-2449. [Full Text]  

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