8PJG

F11 TCR in complex with Human Leukocyte Antigen class II allotype DR1 presenting P11T->R modified influenza A virus haemagglutinin (HA)306-318 PKYVKQNTLKLAR

Summary for 8PJG

• Entry DOI: 10.2210/pdb8pjg/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1 beta chain, Hemagglutinin HA2 chain, ... (8 entities in total)
• Functional Keywords: hla-ii, hla-dr, hla-dr1, human leukocyte antigen, major histocompatibility complex, major histocompatibility complex class 2, influenza a virus, flu, haemagglutinin, ha, infection, vaccine, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 96610.40

Authors

MacLachlan, B.J.,Wall, A.,Greenshields-Watson, A.L.,Cole, D.K.,Rizkallah, P.J.,Godkin, A.J. (deposition date: 2023-06-23, release date: 2024-06-19, Last modification date: 2024-10-16)

Primary citation

Hulin-Curtis, S.,Geary, J.K.,MacLachlan, B.J.,Altmann, D.M.,Baillon, L.,Cole, D.K.,Greenshields-Watson, A.,Hesketh, S.J.,Humphreys, I.R.,Jones, I.M.,Lauder, S.N.,Mason, G.H.,Smart, K.,Scourfield, D.O.,Scott, J.,Sukhova, K.,Stanton, R.J.,Wall, A.,Rizkallah, P.J.,Barclay, W.S.,Gallimore, A.,Godkin, A.
A targeted single mutation in influenza A virus universal epitope transforms immunogenicity and protective immunity via CD4 + T cell activation.
Cell Rep, 43:114259-114259, 2024

PubMed Abstract: CD4 T cells are central to adaptive immunity. Their role in cross-protection in viral infections such as influenza and severe acute respiratory syndrome (SARS) is well documented; however, molecular rules governing T cell receptor (TCR) engagement of peptide-human leukocyte antigen (pHLA) class II are less understood. Here, we exploit an aspect of HLA class II presentation, the peptide-flanking residues (PFRs), to "tune" CD4 T cell responses within an in vivo model system of influenza. Using a recombinant virus containing targeted substitutions at immunodominant HLA-DR1 epitopes, we demonstrate limited weight loss and improved clinical scores after heterosubtypic re-challenge. We observe enhanced protection linked to lung-derived influenza-specific CD4 and CD8 T cells prior to re-infection. Structural analysis of the ternary TCR:pHLA complex identifies that flanking amino acids influence side chains in the core 9-mer peptide, increasing TCR affinity. Augmentation of CD4 T cell immunity is achievable with a single mutation, representing a strategy to enhance adaptive immunity that is decoupled from vaccine modality.

PubMed: 38819988
DOI: 10.1016/j.celrep.2024.114259

Experimental method

X-RAY DIFFRACTION (1.83 Å)