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Natural killer cell recognition of target cells expressing different antigens of vesicular stomatitis virus



Natural killer cell recognition of target cells expressing different antigens of vesicular stomatitis virus



Proceedings of the National Academy of Sciences of the United States of America 82(8): 2456-2459



Natural killer (NK) cells have the capability of lysing virus-infected, transformed and embryonal cells, yet the nature of the target structure(s) recognized remains unclear. The availability of well-characterized temperature-sensitive (ts) mutants of vesicular stomatitis virus, defective in expression of individual viral-encoded polypeptides at the nonpermissive temperature (39.degree. C), offered an approach to elucidating NK-cell recognition of virus-infected cells. Target cells were infected with ts mutants in 3 functions: the viral surface glycoprotein (G protein; ts 045); the matrix (M) protein (ts G31, ts G33), and the polymerase (ts G11). Cells infected with wild-type virus and all ts mutants at the permissive temperature (31.degree. C) were killed by murine spleen cells. Similar to results on cytotoxic T lymphocytes, target cells infected by ts 045 defective in expression of G protein at 39.degree. C were not killed by NK cells. Cells infected at 39.degree. C with M-protein mutants also were not killed, although G protein was expressed at the cell surface. Target binding studies indicated that conjugates were not formed by cells infected with the ts mutants at the nonpermissive temperature. That expression of G protein was not sufficient for NK cell-mediated cytotoxicity was established in experiments in which a plasmid (pSVGL) containing the gene for vesicular stomatitis virus G protein was transfected into COS cells. Although G antigen was expressed on the plasma membrane, the cells were not lysed. These results suggest either that recognition of virus-infected cells depends on an appropriate conformation imparted to the viral G protein by association with the M protein or that NK cells can recognize alterations in the structure of the cell membrane induced by insertion of viral M and G molecules.

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Accession: 005959007

Download citation: RISBibTeXText

PMID: 2986117

DOI: 10.2307/25118


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