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Studies on the antigenicity of the NKG2D ligand H60a in tumour cells

机译:NKG2D配体H60a在肿瘤细胞中的抗原性研究

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摘要

H60a is a minor histocompatibility antigen expressed in BALB and 129/Sv but not C57BL/6 mouse strains. The majority of CD8+ T cells in C57BL/6 mice responding to BALB.B splenocytes are specific for H60a. Interestingly, H60a is expressed constitutively on tumour cells, but its nature as a tumour rejection antigen, as a parallel to its function as a transplant rejection antigen, has not been studied. In this report, we show that tumour cells that constitutively express H60a at the cell surface can be recognized by H60a-specific T cells. Furthermore, when H60a-expressing sarcoma cell lines are transplanted into C57BL/6 mice, H60a-specific T cells can be found at high percentages among the tumour-infiltrating CD8+ T cells. These findings were seen in C57BL/6 but not F1 (C57BL/6 × 129) mice (which express H60a), suggesting that endogenous tolerance mechanisms suppress the antigenic properties of H60a. Our findings have implications for the generation of tumour vaccines against human natural killer group 2D ligands, such as MHC class I chain-like gene A, that are also transplantation antigens.
机译:H60a是在BALB和129 / Sv中表达的次要组织相容性抗原,但在C57BL / 6小鼠品系中不表达。 C57BL / 6小鼠中大多数对BALB.B脾脏应答的CD8 + T细胞对H60a具有特异性。有趣的是,H60a在肿瘤细胞上组成性表达,但尚未研究其作为肿瘤排斥抗原的性质,与其作为移植排斥抗原的功能平行。在这份报告中,我们显示了在细胞表面组成性表达H60a的肿瘤细胞可以被H60a特异性T细胞识别。此外,当将表达H60a的肉瘤细胞系移植到C57BL / 6小鼠中时,可以在肿瘤浸润的CD8 + T细胞中以很高的百分比发现H60a特异性T细胞。这些发现见于C57BL / 6小鼠,而不是F1(C57BL / 6×129)小鼠(表达H60a),表明内源耐受机制抑制了H60a的抗原特性。我们的发现对针对人类自然杀手组2D配体(例如MHC I类链状基因A)的肿瘤疫苗的产生具有重要意义,它们也是移植抗原。

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