Cutting edge: adenovirus E19 has two mechanisms for affecting class I MHC expression.
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. DeltaE19, 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.
Bennett
E M
EM
The G.W. Hooper Foundation, Department of Microbiology and Immunology, University of California, San Francisco 94143, USA.
Bennink
J R
JR
Yewdell
J W
JW
Brodsky
F M
FM
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000502:physiology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001402:B-Lymphocytes; D002461:Cell Line, Transformed; D006680:HLA Antigens / Q000096:biosynthesis* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D017503:Adenovirus E3 Proteins; C084390:E3 glycoprotein 19k, Adenovirus type 7; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human