HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV
Name
1-s2.0-S2211124721007762-main.pdf
Description
Published version
Size
3.69 MB
Format
Adobe PDF
Checksum (MD5)
29bb49fbad0fda34dcd9981bc102ac14
Author(s)
Kaseke, Clarety
Park, Ryan J
Singh, Nishant K
Koundakjian, Dylan
Bashirova, Arman
Garcia Beltran, Wilfredo F
Takou Mbah, Overbeck C
Ma, Jiaqi
Senjobe, Fernando
Urbach, Jonathan M
Date Issued
July 2021
Journal
Cell Reports
Publisher
Elsevier BV
Version
Final published version
Abstract
Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes. HLA class-I-peptide stability is also strongly correlated with overall immunodominance hierarchies, particularly for epitopes from high-abundance proteins (e.g., Gag). Moreover, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions at a greater frequency than neutral and risk alleles. These findings indicate that relative stabilization of HLA class-I is a key factor for CD8+ T cell epitope immunodominance hierarchies, with implications for HIV control and the design of T-cell-based vaccines.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2021.109378
