HLA-E-restricted recognition of cytomegalovirus-derived peptides by human CD8+ cytolytic T lymphocytes |
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Authors: | Pietra Gabriella Romagnani Chiara Mazzarino Paola Falco Michela Millo Enrico Moretta Alessandro Moretta Lorenzo Mingari Maria Cristina |
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Affiliation: | Istituto Giannina Gaslini, 16147 Genova, Italy. |
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Abstract: | HLA-E-restricted T cell receptor alphabeta+ CD8+ cytolytic T lymphocytes (CTLs) exist as monoclonal expansions in the peripheral blood of some individuals. Here, we show that they recognize, with high avidity, peptides derived from the UL40 protein of different human cytomegalovirus (CMV) strains. Recognition results in the induction of cytotoxicity, IFN-gamma production and cell proliferation. Autologous cells pulsed with CMV-derived peptides become susceptible to lysis by HLA-E-restricted CTLs and induce their proliferation. The high avidity for CMV-derived peptides may explain how these cells are generated in vivo and suggest their possible role in the host defenses against CMV, a virus that evolved various mechanisms to down-regulate classical HLA class I molecules, thus escaping detection by conventional CTLs. |
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