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


METHODS
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.
Tykodi
Scott S
SS
Program in Immunology, Fred Hutchinson Cancer Research Center.
Fujii
Nobuharu
N
Vigneron
Nathalie
N
Lu
Sharon M
SM
Mito
Jeffrey K
JK
Miranda
Maureen X
MX
Chou
Jeffrey
J
Voong
Lilien N
LN
Thompson
John A
JA
Sandmaier
Brenda M
BM
Cresswell
Peter
P
Van den Eynde
Benoît
B
Riddell
Stanley R
SR
Warren
Edus H
EH
D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D045744:Cell Line, Tumor; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015723:Gene Library; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens