Conserved amino acids within the adenovirus 2 E3/19K protein differentially affect downregulation of MHC class I and MICA/B proteins

The Journal of Immunology : Official Journal of the American Association of Immunologists
Martina SesterHans-Gerhard Burgert

Abstract

Successful establishment and persistence of adenovirus (Ad) infections are facilitated by immunosubversive functions encoded in the early transcription unit 3 (E3). The E3/19K protein has a dual role, preventing cell surface transport of MHC class I/HLA class I (MHC-I/HLA-I) Ags and the MHC-I-like molecules (MHC-I chain-related chain A and B [MICA/B]), thereby inhibiting both recognition by CD8 T cells and NK cells. Although some crucial functional elements in E3/19K have been identified, a systematic analysis of the functional importance of individual amino acids is missing. We now have substituted alanine for each of 21 aas in the luminal domain of Ad2 E3/19K conserved among Ads and investigated the effects on HLA-I downregulation by coimmunoprecipitation, pulse-chase analysis, and/or flow cytometry. Potential structural alterations were monitored using conformation-dependent E3/19K-specific mAbs. The results revealed that only a small number of mutations abrogated HLA-I complex formation (e.g., substitutions W52, M87, and W96). Mutants M87 and W96 were particularly interesting as they exhibited only minimal structural changes suggesting that these amino acids make direct contacts with HLA-I. The considerable number of substi...Continue Reading

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Feb 9, 2011·Immunology and Cell Biology·Daniëlle HorstEmmanuel J H J Wiertz
Oct 9, 2012·Nature Structural & Molecular Biology·Lenong LiMarlene Bouvier
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Feb 9, 2021·PloS One·Mariya LazarovaAlexander Steinle

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