C19orf48 Encodes a Minor Histocompatibility Antigen Recognized by CD8+ Cytotoxic T Cells from Renal Cell Carcinoma Patients

SS Tykodi, N Fujii, N Vigneron, SM Lu, JK Mito… - Clinical cancer …, 2008 - AACR
SS Tykodi, N Fujii, N Vigneron, SM Lu, JK Mito, MX Miranda, J Chou, LN Voong
Clinical cancer research, 2008AACR
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 …
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.
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