Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells
Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells
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DOI：
10.4049/jimmunol.174.5.2661
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Wang, RF
中科院分区：
文献类型：
--
作者：
Wang, HY;Peng, GY;Wang, RF
CD4（+）调节性T （Treg）细胞通过抑制自身免疫性疾病和癌症的免疫应答，在维持免疫自身耐受中发挥重要作用。然而，对优先激活CD4(+) Treg细胞的天然抗原配体知之甚少。在此，我们报道了从肿瘤患者的肿瘤浸润淋巴细胞（til）中建立肿瘤特异性CD4(+) Treg细胞克隆，并鉴定了Treg细胞（ARTC1）识别的Ag基因，该基因编码肿瘤特异性TIL164 CD4(+) Treg细胞识别的肽配体。在164mel肿瘤细胞中，一个编码ARTC1的基因突变导致含有CD4(+) Treg细胞识别的肽配体的基因产物的翻译。ARM肽激活的CD4(+) Treg细胞抑制黑色素瘤反应性T细胞的生理功能（增殖和IL-2分泌）。此外，164mel肿瘤细胞，而不是B细胞上的肿瘤裂解物，能够激活TIL164 CD4(+) Treg细胞。这些结果表明，肿瘤细胞可能独特地呈现一系列肽配体，这些肽配体优先招募和激活肿瘤特异性自我肽表达部位的CD4(+) Treg细胞，从而诱导局部和肿瘤特异性免疫抑制。
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. ARM 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.