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HLA class-I-peptide stability mediates CD8(+) T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV

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...

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Detalles Bibliográficos
Autores principales: 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., Nathan, Anusha, Rossin, Elizabeth J., Tano-Menka, Rhoda, Khatri, Ashok, Piechocka-Trocha, Alicja, Waring, Michael T., Birnbaum, Michael E., Baker, Brian M., Carrington, Mary, Walker, Bruce D., Gaiha, Gaurav D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293625/
https://www.ncbi.nlm.nih.gov/pubmed/34260940
http://dx.doi.org/10.1016/j.celrep.2021.109378
Descripción
Sumario: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.