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C19orf48 Encodes a Minor Histocompatibility Antigen Recognized by CD8⁺ Cytotoxic T Cells from Renal Cell Carcinoma Patients

Authors' Affiliations: ¹ Program in Immunology, Fred Hutchinson Cancer Research Center; ² Department of Medicine, University of Washington, Seattle, Washington; ³ Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut; ⁴ Ludwig Institute for Cancer Research, Brussels Branch; and ⁵ Cellular Genetics Unit, Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium

Requests for reprints: Edus H. Warren, Program in Immunology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, P.O. Box 19024, Seattle, WA 98109-1024. Phone: 206-667-6441; Fax: 206-667-7983; E-mail: ehwarren{at}u.washington.edu.

Purpose: Tumor regression has been observed in some patients with metastatic renal cell carcinoma (RCC) after nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). Cellular and molecular characterization of antigens recognized by tumor-reactive T cells isolated from responding patients could potentially provide insight into the mechanisms of tumor regression.

Experimental Design: CD8⁺ CTL clones that recognized a novel RCC-associated minor histocompatibility (H) antigen presented by HLA-A*0201 were isolated from two patients with metastatic RCC who experienced tumor regression or stable disease following nonmyeloablative allogeneic HCT. These clones were used to screen a cDNA library and isolate the unique cDNA encoding the antigen.

Results: An alternative open reading frame in the C19orf48 gene located on chromosome 19q13 encodes the HLA-A*0201–restricted minor H antigen recognized by the RCC-reactive T cells. The differential T-cell recognition of donor- and recipient-derived target cells is attributable to a nonsynonymous single-nucleotide polymorphism within the nucleotide interval that encodes the antigenic peptide. Assays for gene expression and CTL recognition showed that the C19orf48-encoded peptide is widely expressed in renal tumors and solid tumors of other histologies. The antigenic peptide can be processed for CTL recognition via both TAP-dependent and TAP-independent pathways.

Conclusions: Donor T-cell responses against the HLA-A*0201–restricted minor H antigen encoded by C19orf48 may contribute to RCC regression after MHC-matched allogeneic HCT.

Commentary

Targets of Tumor Immunity After Allogeneic Hematopoietic Stem Cell Transplantation

Yishay Ofran and Jerome Ritz
Clin. Cancer Res. 2008 14: 4997-4999. [Abstract] [Full Text] [PDF]

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				Y. Ofran and J. Ritz Targets of Tumor Immunity After Allogeneic Hematopoietic Stem Cell Transplantation Clin. Cancer Res., August 15, 2008; 14(16): 4997 - 4999. [Abstract] [Full Text] [PDF]