RT Journal Article
SR Electronic
T1 Cutting Edge: Adenovirus E19 Has Two Mechanisms for Affecting Class I MHC Expression<sup>1</sup>
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 5049
OP 5052
VO 162
IS 9
A1 Bennett, Elizabeth M.
A1 Bennink, Jack R.
A1 Yewdell, Jonathan W.
A1 Brodsky, Frances M.
YR 1999
UL http://www.jimmunol.org/content/162/9/5049.abstract
AB Viral strategies for immune evasion include inhibition of various steps in the class I MHC assembly pathway. Here, we demonstrate that adenovirus produces one gene product with a dual function in this regard. It is well established that adenovirus E19 binds class I molecules and retains them in the endoplasmic reticulum (ER). However, E19 also delays the expression of class I alleles to which it cannot tightly bind. Here, we show that E19 binds TAP and acts as a tapasin inhibitor, preventing class I/TAP association. ΔE19, an E19 mutant lacking the ER-retention signal, delays maturation of class I molecules, indicating that E19’s inhibition of class I/TAP interaction is sufficient to delay class I expression. These data identify tapasin inhibition as a novel mechanism of viral immune evasion and suggest that, through this secondary mechanism, adenovirus can affect Ag presentation by MHC alleles that it can only weakly affect by direct retention.