Monoclonal antibodies were produced to JHMV-DL, a neurotropic member of the mouse hepatitis virus (MHV) or murine coronavirus group. Of 23 antibodies isolated, 10 were specific for the major envelope glycoprotein, gp180/90, 10 for the nucleocapsid protein, pp60, and 3 for the minor envelope glycoprotein, gp25. Eleven different MHV isolates were used in antibody binding assays to study antigenic relationships among the viruses. Each MHV isolate tested had a unique pattern of antibody binding, indicating that each is a distinct strain. Conservation of JHMV-DL antigenic determinants varied among the three proteins, with pp60 showing intermediate conservation, gp180/90 little conservation, and gp25 marked conservation in the different MHV strains. Monoclonal antibodies to pp60 proved most useful in delineating antigenic relationships among MHV strains. These antigenic groups correlated with pathogenic types, indicating that pp60 may be one of the gene products which mediates the distinct disease patterns manifested by different murine coronaviruses.

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The ability of the JHM3 strain of mouse hepatitis virus (MHV) to induce natural killer (NK) cells was examined. Infection of C57BL/6 (B6) mice with this virus resulted in the augmentation of natural cytotoxicity against YAC-I target cells in the absence of a detectable interferon response. The cells responsible for this increased cytotoxicity were sensitive to complement-mediated lysis with an anti-Q-5 reagent but not with a Thy 1.2 antiserum, indicating that they possess an NK-like surface phenotype. Although variation in the NK response of individual B6 mice following JHM virus infection was found, even the animal with the most responsive NK cell population had no detectable interferon in the spleen. This finding contrasted with observations with an unrelated virus (lymphocytic choriomeningitis virus) and a serologically related strain of MHV. Infection with both of these viruses induced augmented NK cell activity and interferon responses. In addition, we found that neither the ability to mount an augmented NK cell response nor preferential lysis of virus-infected targets correlated with resistance or susceptibility to JHM virus infection.

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Mouse L cells transfected with a genomic clone containing the H-2Ld gene (8-5 cells) were shown to function as targets for H-2Ld-specific cytotoxic T lymphocytes (CTL). The CTL-mediated lysis of 8-5 cells was shown to be H-2Ld specific by the use of(i) CTL with restricted reactivity, (ii) unlabeled target inhibition, and (iii) monoclonal antibody inhibition. We also demonstrated that 8-5 cells could function as targets for antibody-pluscomplement-mediated cell lysis. Specificity was confirmed by using H-2Ld-specific monoclonal antibodies. These experiments demonstrate that the gene products of a major histocompatibility complex genomic clone can be functionally expressed in a foreign cell and can mediate immunologically specific cellular interactions.