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

Clin Cancer Res. 2008 Aug 15;14(16):5260-9. doi: 10.1158/1078-0432.CCR-08-0028.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Minor Histocompatibility Antigens