The putative natural killer decoy early gene m04 (gp34) of murine cytomegalovirus encodes an antigenic peptide recognized by protective antiviral CD8T cells

Several early genes of murine cytomegalovirus (MCMV) encode proteins that m ediate immune evasion by interference with the major histocompatibility com plex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphoc ytes (CTL). Specifically, the m152 gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compa rtment. Lack of MHC-I on the cell surface should activate natural killer (N K) cells recognizing the "missing self." The retention, however, is counter acted by the m04 early gene product gp34, which binds to folded MHC-I molec ules in the ER and directs the complex to the cell surface. It was thus spe culated that gp34 might serve to silence NK cells and thereby complete the immune evasion of MCMV. In light of these current views, we provide here re sults demonstrating an in vivo role for gp34 in protective antiviral immuni ty. We have identified an antigenic nonapeptide derived from gp34 and prese nted by the MHC-I molecule Dd. Besides the immunodominant immediate-early n onapeptide consisting of IE1 amino acids 168-176 (IE1(168-176)), the early nonapeptide m04(243-251) is the second antigenic peptide described for MCMV . The primary immune response to :MCMV generates significant m04-specific C D8 T-cell memory. Upon adoptive transfer into immunodeficient recipients, a n m04-specific CTL line controls MCMV infection with an efficacy comparable to that of an IE1-specific CTL line. Thus, gp34 is the first noted early p rotein of MCMV that escapes viral immune evasion mechanisms. These data doc ument that MCMV is held in check by a redundance of protective CD8 T cells recognizing antigenic peptides in different phases of viral gene expression .