Cutting Edge: Adenovirus E19 Has Two Mechanisms for Affecting Class I MHC Expression1

• Published in: The Journal of immunology (1950) Vol. 162; no. 9; pp. 5049 - 5052
• Main Authors: Bennett, Elizabeth M, Bennink, Jack R, Yewdell, Jonathan W, Brodsky, Frances M
• Format: Journal Article
• Language: English
• Published: Am Assoc Immnol 01.05.1999
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.9.5049

Abstract 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.