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@ARTICLE{Zimmermann:288506,
author = {C. Zimmermann and G. M. Watson and L. Bauersfeld and R.
Berry and B. Ciblis and H. Lan and C. Gerke and V. Oberhardt
and J. Fuchs and M. Hofmann and C. Freund and J. Rossjohn
and F. Momburg$^*$ and H. Hengel and A. Halenius},
title = {{D}iverse cytomegalovirus {US}11 antagonism and {MHC}-{A}
evasion strategies reveal a tit-for-tat coevolutionary arms
race in hominids.},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {121},
number = {9},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {DKFZ-2024-00379},
pages = {e2315985121},
year = {2024},
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.},
keywords = {HLA-A (Other) / MHC class I (Other) / coevolution (Other) /
cytomegalovirus (Other) / tapasin (Other)},
cin = {D120 / D121},
ddc = {500},
cid = {I:(DE-He78)D120-20160331 / I:(DE-He78)D121-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38377192},
doi = {10.1073/pnas.2315985121},
url = {https://inrepo02.dkfz.de/record/288506},
}