Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice.

作者: Françoise Lenfant , Nathalie Pizzato , Siyuan Liang , Christian Davrinche , Philippe Le Bouteiller

DOI: 10.1099/VIR.0.18735-0

关键词:

摘要: The non-classical major histocompatibility complex class I molecule HLA-G is expressed mainly by extravillous trophoblasts at the materno–foetal interface. has been found to bind endogenously processed nonameric peptides but its function as a restriction element for cytotoxic T cell response viruses with tropism trophoblastic cells never demonstrated. In this study, candidate viral derived from human cytomegalovirus (HCMV) pp65 (UL83), which stabilized on HLA-G-transfected T2 cells, were identified. specific anti-pp65 lymphocyte (CTL) restricted in triple transgenic mice (HLA-G, β2m, CD8α) was then investigated injection of dendritic loaded synthetic pp65-derived or infection canarypox virus expressing pp65. Results showed that CTLs have capacity kill target either infected recombinant vaccinia using an antigen-presenting molecule. It also demonstrated these HLA-G-restricted pp65-specific are able astrocytoma line U373, transfected and HCMV. Moreover, tetramers refolded peptide, peptide-specific CD8+ detected vivo. These findings provide first evidence can select anti-HCMV-restricted vivo, although potency cytolytic limited (20–25 %). weak anti-HCMV probably due HLA-G-mediated inhibitory signals development antiviral CTL response.

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