Poxvirus-encoded serpins do not prevent cytolytic T cell-mediated recoveryfrom primary infections

Previous observations that the highly conserved poxvirus-encoded serpins in hibit cytotoxic activities of alloreactive CTL via granule and/or Fas-media ted pathways was taken to indicate their involvement in immune evasion by p oxviruses. We now show that interference with Cr-51 release from target cel ls by ectromelia and cowpoxvirus is limited to alloreactive but not MHC-res tricted CTL. The data are in support of the paramount importance of CTL and its effector molecule perforin in the recovery from primary ectromelia vir us infection and question the role of serpins in the evasion of poxviruses from killing by CTL, Further analysis of poxvirus interference with target cell lysis by alloreactive CTL revealed that suppression primarily affects the Fas-mediated, and to a lesser extent, the granule exocytosis pathway. S erpin-2 is the main contributor to suppression for both killing pathways, I n addition, inhibition of lysis was shown to be both target cell type- and MHC allotype-dependent. We hypothesize that differences in TCR affinities a nd/or state of activation between alloreactive and MHC-restricted CTL as we ll as the quality (origin) of target cells are responsible for the observed phenomenon.