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Characterization of a Novel Nonclassical T Cell Clone with Broad Reactivity against Human Renal Cell Carcinomas¹

Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

A CD4⁺ T cell clone (HC/2G-1) was established by stimulating peripheral blood T cells from a patient with renal cell carcinoma (RCC) with dendritic cells preincubated with the autologous apoptotic renal tumor line in the presence of IFN-. It recognizes the autologous RCC and most allogeneic RCC lines by IFN- release (10 of 11 lines) and lysis (9 of 10 lines), but does not recognize multiple EBV B cells or fibroblasts. It shows little or no recognition of a panel of melanomas, breast cancers and non-small–cell lung cancers. Phenotypically, HC/2G-1 is CD3⁺CD4⁺ TCR β⁺, but CD161^–CD16^–NKG2D^–. Tumor recognition by clone HC/2G-1 was not blocked by Abs to HLA class I or class II, but was significantly reduced by anti-TCR β Ab. Furthermore, tumor recognition was β₂-microglobulin-independent. HC/2G-1 does not use a V or Vβ described for classical NKT cells, but rather V14 and Vβ2.1. Allogeneic T cells cotransfected with mRNAs encoding the and β chains of the HC/2G-1 TCR recognized renal tumor lines, demonstrating that tumor recognition is TCR-mediated. Interestingly, TRAIL appears to play a role in tumor recognition by HC/2G-1 in that reactivity was blocked by anti-TRAIL Ab, and soluble TRAIL could enhance IFN- secretion by HC/2G-1 in response to renal tumors. Our findings suggest that clone HC/2G-1 represents a novel type of CD4⁺ cell that has broad TCR-mediated recognition of a determinant widely expressed by RCC.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.

² Address correspondence and reprint requests Dr. James C. Yang, Surgery Branch, Center for Cancer Research, National Cancer Institute, Building 10 Clinical Research Center, National Institutes of Health, 9000 Rockville Pike, Room 3W-3840, Bethesda, MD 20892. E-mail address: James_Yang{at}nih.gov

³ Abbreviations used in this paper: RCC, renal cell carcinoma; HRE, human renal epithelial; DC, dendritic cell; β₂m, β₂-microglobulin; TRAIL, TNF-related apoptosis-inducing ligand.