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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.

Original publication

DOI

10.1158/1078-0432.CCR-08-0028

Type

Journal article

Journal

Clin Cancer Res

Publication Date

15/08/2008

Volume

14

Pages

5260 - 5269

Keywords

Antigens, Neoplasm, Base Sequence, CD8-Positive T-Lymphocytes, Carcinoma, Renal Cell, Cell Line, Tumor, Chromosomes, Human, Pair 19, Epitopes, T-Lymphocyte, Gene Library, HLA-A Antigens, HLA-A2 Antigen, Hematopoietic Stem Cell Transplantation, Humans, Kidney Neoplasms, Minor Histocompatibility Antigens, Molecular Sequence Data, Polymorphism, Single Nucleotide, Reverse Transcriptase Polymerase Chain Reaction, Transfection, Transplantation, Homologous