CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED CYTOTOXIC T-LYMPHOCYTES ARE NOT NECESSARY FOR HETEROTYPIC IMMUNITY TO INFLUENZA

Mice transgenic for beta(2)-microglobulin deletion (beta(2)M-/-) were immunized intranasally with either a recombinant vaccinia virus that expressed both nucleoprotein and interleukin-2 or by infection with H3N2 influenza virus; 3-4 weeks later they were challenged with H1N1 influenza virus. The immunized beta(2)M-/- mice had increased survival and enhanced clearance of virus relative to nonimmune controls. This protection correlated with the development of class II major histocompatibility complex-restricted pulmonary cytotoxic T lymphocyte activity and nasal IgA anti-nucleoprotein antibody. Heterotypic immunity can therefore be generated by a mechanism that does not involve class I major histocompatibility complex-restricted T cells.