C19orf48 encodes a minor histocompatibility antigen recognized by CD8 + cytotoxic T cells from renal cell carcinoma patients

Scott S. Tykodi, Nobuharu Fujii, Nathalie Vigneron, Sharon M. Lu, Jeffrey K. Mito, Maureen X. Miranda, Jeffrey Chou, Lilien N. Voong, John A. Thompson, Brenda M. Sandmaier, Peter Cresswell, Benoît Den Van Eynde, Stanley R. Riddel, Edus H. Warren

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Abstract

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-reactiveT 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-reactiveT 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

Original languageEnglish
Pages (from-to)5260-5269
Number of pages10
JournalClinical Cancer Research
Volume14
Issue number16
DOIs
Publication statusPublished - Aug 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tykodi, S. S., Fujii, N., Vigneron, N., Lu, S. M., Mito, J. K., Miranda, M. X., Chou, J., Voong, L. N., Thompson, J. A., Sandmaier, B. M., Cresswell, P., Van Eynde, B. D., Riddel, S. R., & Warren, E. H. (2008). C19orf48 encodes a minor histocompatibility antigen recognized by CD8 + cytotoxic T cells from renal cell carcinoma patients. Clinical Cancer Research, 14(16), 5260-5269. https://doi.org/10.1158/1078-0432.CCR-08-0028