Asset Details
Do you wish to reserve the book?
Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
Do you wish to request the book?
Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Paper
Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
2023
Overview
To control human cytomegalovirus (HCMV) infection, NK cells and CD8+ T-cells are crucial. HLA class I (HLA-I) molecules play a central role for both NK and T-cell responses and are targets of multifaceted HCMV-encoded immunoevasins. A so far insufficiently studied HLA-I immunoevasin is the glycoprotein US10. It was shown that US10 targets HLA-G, but it is unknown whether US10 contributes also to escape from classical HLA-I antigen presentation. Our biochemical analysis revealed that early during maturation, all investigated HLA-I (HLA-A/B/C/E/G) heavy chains are recognized and bound by US10. Remarkably, the consequences of this initial binding strongly depended on both the HLA-I geno- and allotypes: i) HLA-A molecules escaped down-regulation by US10, ii) tapasin-dependent HLA-B molecules exhibited impaired recruitment to the peptide loading complex and maturation, iii) HLA-C and HLA-G, but not HLA-A/B/E, strongly bound US10 also in their β2m-assembled form. Thus, US10 senses geno- and allotypic differences in a so far unparalleled and multimodal manner, suggestive of adaptation to HLA-I genotype differences. At a further level of complexity, in HCMV-infected fibroblasts inhibition of overlapping US10 and US11 transcription revealed an additional HLA-I specificity, suggesting targeting of HLA-I in a synergistically arranged manner. Our study unveils the exceptional HLA-I selectivity of HCMV-encoded US10 and underlines its contribution to immune escape.Competing Interest StatementThe authors have declared no competing interest.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
