Identification of a naturally processed HLA‐Cw7‐binding peptide that cross‐reacts with HLA‐A24‐restricted ovarian cancer‐specific CTLs. Issue 3 (28th July 2015) - Yamada, E.
Abstract Here, we describe an human leukocyte antigen (HLA)‐A*24:02‐restricted cytotoxic T‐lymphocyte (CTL) clone, 1G3, established from naïve CD8+ T‐lymphocytes obtained from a healthy donor stimulated with HLA‐modified TOV21G, an ovarian cancer cell line. The 1G3 clone responds not only to ovarian cancer cells in the context of HLA‐A*24:02 but also to allogeneic HLA‐Cw*07:02 molecules through cross‐reactive T‐cell receptor recognition. Expression screening using a complementary DNA library constructed from TOV21G messenger RNA revealed that this alloreactivity was mediated through the nine‐mer peptide VRTPYTMSY, derived from RNA‐binding motif protein 4. To our knowledge, this study presents the first example of the allorecognition of an HLA‐Cw molecule by HLA‐A‐restricted T‐cells, thereby revealing a naturally processed epitope peptide. These findings provide the structural bases for the allorecognition of human T‐cells. In addition, this study suggests that unexpected alloresponses occur in certain HLA combinations, and further study is needed to understand the mechanisms of alloreactivity for better prediction of alloresponses in clinical settings.