Dataset Information

Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning

ABSTRACT: HLA class I (HLA-I) molecules play a central role for both NK and T-cell responses that prevent serious human cytomegalovirus (HCMV) disease. To create opportunities for viral spread, multifaceted HCMV-encoded immunoevasins target HLA-I. Among these, the glycoprotein US10 is so far insufficiently studied. While US10 has been shown to interfere with HLA-G expression, its ability to block classical HLA-I antigen presentation remains unknown. In this study, we demonstrate that US10 recognizes and binds to all HLA-I (HLA-A,-B,-C,-E,-G) heavy chains. Additionally, impaired recruitment of HLA-I to the peptide loading complex was observed. Notably, the associated effects varied significantly dependent on HLA-I genotype and allotype: i) HLA-A molecules evaded down-regulation by US10, ii) tapasin-dependent HLA-B molecules showed impaired maturation and cell surface expression, iii) β2m-assembled HLA-C, in particular HLA-C*05:01 and -C*12:03, and HLA-G were strongly retained in complex with US10 in the endoplasmic reticulum. These genotype-specific effects on HLA-I were confirmed through unbiased HLA-I ligandome analysis. Thus, the US10-mediated impact on HLA-I results in geno- and allotypic differences in a so far unparalleled and multimodal manner.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Chiara Noemi-Marie Mireisz

LAB HEAD: Andreas Schlosser

PROVIDER: PXD051190 | Pride | 2024-07-03

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2023-09-04_Fusion_39176.raw	Raw
	2023-09-04_Fusion_39177.raw	Raw
	HeLa_US10.xlsx	Xlsx

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Publications

Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning.

Gerke Carolin C Bauersfeld Liane L Schirmeister Ivo I Mireisz Chiara Noemi-Marie CN Oberhardt Valerie V Mery Lea L Wu Di D Jürges Christopher Sebastian CS Spaapen Robbert M RM Mussolino Claudio C Le-Trilling Vu Thuy Khanh VTK Trilling Mirko M Dölken Lars L Paster Wolfgang W Erhard Florian F Hofmann Maike M Schlosser Andreas A Hengel Hartmut H Momburg Frank F Halenius Anne A

eLife 20240620

Human leucocyte antigen class I (HLA-I) molecules play a central role for both NK and T-cell responses that prevent serious human cytomegalovirus (HCMV) disease. To create opportunities for viral spread, several HCMV-encoded immunoevasins employ diverse strategies to target HLA-I. Among these, the glycoprotein US10 is so far insufficiently studied. While it was reported that US10 interferes with HLA-G expression, its ability to manipulate classical HLA-I antigen presentation remains unknown. In ...[more]

PMID: 38900146

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