Journal Article

DKFZ-2024-00379

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Diverse cytomegalovirus US11 antagonism and MHC-A evasion strategies reveal a tit-for-tat coevolutionary arms race in hominids.

Zimmermann, C. ; Watson, G. M. ; Bauersfeld, L. ; Berry, R. ; Ciblis, B. ; Lan, H. ; Gerke, C. ; Oberhardt, V. ; Fuchs, J. ; Hofmann, M. ; Freund, C. ; Rossjohn, J. ; Momburg, F.DKFZ* ; Hengel, H. ; Halenius, A.

2024
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.2315985121

Abstract: Recurrent, ancient arms races between viruses and hosts have shaped both host immunological defense strategies as well as viral countermeasures. One such battle is waged by the glycoprotein US11 encoded by the persisting human cytomegalovirus. US11 mediates degradation of major histocompatibility class I (MHC-I) molecules to prevent CD8+ T-cell activation. Here, we studied the consequences of the arms race between US11 and primate MHC-A proteins, leading us to uncover a tit-for-tat coevolution and its impact on MHC-A diversification. We found that US11 spurred MHC-A adaptation to evade viral antagonism: In an ancestor of great apes, the MHC-A A2 lineage acquired a Pro184Ala mutation, which confers resistance against the ancestral US11 targeting strategy. In response, US11 deployed a unique low-complexity region (LCR), which exploits the MHC-I peptide loading complex to target the MHC-A2 peptide-binding groove. In addition, the global spread of the human HLA-A*02 allelic family prompted US11 to employ a superior LCR strategy with an optimally fitting peptide mimetic that specifically antagonizes HLA-A*02. Thus, despite cytomegaloviruses low pathogenic potential, the increasing commitment of US11 to MHC-A has significantly promoted diversification of MHC-A in hominids.

Keyword(s): HLA-A ; MHC class I ; coevolution ; cytomegalovirus ; tapasin

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Contributing Institute(s):

1. Angewandte Tumor-Immunität (D120)
2. AG Antigenpräsentation und T/NK-Zell-Akt (D121)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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