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

• DOI: 10.1016/j.celrep.2021.109378
• Publication Date: 2021-07-13T15:10:58Z
• Authors: Clarety Kaseke; Ryan J. Park; Nishant K. Singh; Dylan Koundakjian; Arman Bashirova; Wilfredo F. Garci...; Overbeck C. Takou...; Jiaqi Ma; Fernando Senjobe; Jonathan M. Urbach; Anusha Nathan; Elizabeth J. Rossin; Rhoda Tano-Menka; Ashok Khatri; Alicja Piechocka-...; Michael T. Waring; Michael E. Birnbaum; Brian M. Baker; Mary Carrington; Bruce D. Walker; Gaurav D. Gaiha
• Keywords: Immunodominance; Subdominant; HLA-A

Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines viral pathogens. Here, we assess contribution human leukocyte antigen (HLA) class-I-peptide stability 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with processing (TAP)-deficient mono-allelic HLA-expressing lines. We find immunodominant increase surface stabilization class-I molecules in comparison to subdominant epitopes. also strongly correlated overall hierarchies, particularly from high-abundance proteins (e.g., Gag). Moreover, protection are preferentially stabilized by derived topologically important regions at a greater frequency than neutral and risk alleles. These findings indicate relative key factor epitope implications control T-cell-based vaccines.