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

Tykodi, Scott S and Fujii, Nobuharu and Vigneron, Nathalie and Lu, Sharon M and Mito, Jeffrey K and Miranda, Maureen X and Chou, Jeffrey and Voong, Lilien N and Thompson, John A and Sandmaier, Brenda M and Cresswell, Peter and Van den Eynde, Benoît and Riddell, Stanley R and Warren, Edus H (2008) C19orf48 encodes a minor histocompatibility antigen recognized by CD8+ cytotoxic T cells from renal cell carcinoma patients. Clinical cancer research : an official journal of the American Association for Cancer Research, 14 (16). pp. 5260-5269. ISSN 1078-0432

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Article URL: http://clincancerres.aacrjournals.org/cgi/reprint/...

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-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.

Item Type: Article
Additional Information: This article is available to subscribers only via the URL above for the first 12 months post-publication.
DOI: 10.1158/1078-0432.CCR-08-0028
PubMed ID: 18698046
NIHMSID: NIHMS104972
PMCID: PMC2693478
Grant Numbers: K08 CA121912-03, R01 CA106512-05, P01 CA078902-10
Keywords or MeSH Headings: Antigens, Neoplasm/genetics/immunology; Base Sequence; CD8-Positive T-Lymphocytes/immunology; Carcinoma, Renal Cell/genetics/immunology/therapy; Cell Line, Tumor; Chromosomes, Human, Pair 19/genetics; Epitopes, T-Lymphocyte/genetics/immunology; Gene Library; HLA-A Antigens/immunology; Hematopoietic Stem Cell Transplantation; Humans; Kidney Neoplasms/genetics/immunology/therapy; Minor Histocompatibility Antigens/genetics/immunology; Molecular Sequence Data; Polymorphism, Single Nucleotide; Reverse Transcriptase Polymerase Chain Reaction; Transfection; Transplantation, Homologous;
Subjects: Diseases > Solid tumors > Kidney cancer
Therapeutics > Transplantation > Stem Cell transplantation
Molecules > Antigens > HLA antigens
Depositing User: Library Staff
Date Deposited: 24 Mar 2009 18:17
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/262

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