Searching for MHC-restricted anti-viral antibodies: antibodies recognizing the nucleoprotein of influenza virus dominate the serological response of C57BL/6 mice to syngeneic influenza-infected cells.

An attempt has been made to generate monoclonal antibodies which recognize the same target structures on influenza-infected cells as those seen by cytotoxic T lymphocyte (CTL) receptors. Such antibodies, if they mimicked the T cell receptor specificity, would be expected to be both virus specific and restricted in their binding by the major histocompatibility complex (MHC) antigens. Approximately 200 hybridomas from C57BL/6 (H-2b) mice primed and boosted with influenza virus (X-31)-infected EL4 (a C57BL/6 T cell lymphoma) were screened for reactivity on infected and uninfected cells of different MHC haplotypes. Of the 10 hybridoma antibodies which were identified as being reactive with X-31-infected EL4, but not uninfected EL4, all reacted equally well with X-31-infected cells of H-2b, H-2d and H-2k haplotypes, indicating a lack of MHC restriction in their recognition of the infected cells. Unexpectedly, 7 of the 10 monoclonal antibodies were found to react specifically with the purified influenza virus nucleoprotein (NP), a predominant viral antigen in CTL recognition of infected cells. Fluorescence-activated flow cytometry confirmed that these antibodies were able to recognize NP serological determinants on the surface of viable, infected cells, but the anti-NP antibodies were unable to block the lytic activity of an NP-specific CTL clone.