Del Val, Margarita and Hengel, Hartmut and Häcker, Hans and Hartlaub, Udo and Ruppert, Thomas and Lucin, Pero and Koszinowski, Ulrich H.
Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment.
In: The journal of experimental medicine, Vol. 176: pp. 729-738
Selective expression of murine cytomegalovirus (MCMV) immediate-early (IE) genes leads to
the presentation by the major histocompatibility complex (MHC) class I molecule L a of a
peptide derived from MCMV IE protein pp89 (Reddehase, M. J., J. B. Rothbard, and U. H.
Koszinowski. 1989. Nature (Lond.). 337:651). Characterization of endogenous antigenic peptides
identified the pp89 peptide as the nonapeptide msYPHFMFFNLt76 (del Val, M., H.-J. Schlicht,
T. Ruppert, M. J. Reddehase, and U. H. Koszinowski. 1991. Cell. 66:1145). Subsequent expression
of MCMV early genes prevents presentation of pp89 (del Val, M., K. Mfinch, M. J. Reddehase,
and U. H. Koszinowski. 1989. Cell. 58:305). We report on the mechanism by which MCMV
early genes interfere with antigen presentation. Expression of the IE promoter-driven bacterial
gene lacZ by recombinant MCMV subjected antigen presentation of B-galactosidase to the same
control and excluded antigen specificity. The La-dependent presence of naturally processed
antigenic peptides also in nonpresenting cells located the inhibitory function subsequent to the
step of antigen processing. The finding that during the E phase of MCMV gene expression the
MHC class I heavy chain glycosylation remained in an Endo H-sensitive form suggested a block
within the endoplasmic reticulum/c/s-Golgi compartment. The failure to present antigenic peptides
was explained by a general retention of nascent assembled trimolecular MHC class I complexes.
Accordingly, at later stages of infection a significant decrease of surface MHC class I expression
was seen, whereas other membrane glycoproteins remained unaffected. Thus, MCMV E genes
endow this virus with an effective immune evasion potential. These results also indicate that
the formation of the trimolecular complex of MHC dass I heavy chain, ~2-microglobulin, and
the finally trimmed peptide is completed before entering the medial-Golgi compartment.