Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2021-07, Vol.36 (2), p.109378, Article 109378

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •TAP-deficient HLA-expressing cells provide rapid assessment of HLA-peptide stability•Immunodominant HIV CD8+ T cell epitopes are superior stabilizers of HLA molecules•HLA class-I-peptide stability correlates with overall immunodominance hierarchies•Protective HLA alleles are preferentially stabilized by highly networked epitopes Kaseke et al. describe a cell-based HLA-peptide stability assay that leverages TAP-deficient mono-allelic HLA-expressing cell lines. Robust HLA stabilization is a common feature of immunodominant epitopes, and HLA-peptide stability correlates with immunodominance hierarchies. Epitopes derived from topologically constrained regions of the HIV proteome preferentially stabilize protective HLA class-I alleles.