tetano
Editor, Senior Moderator
Nat Commun. 2018 Dec 21;9(1):5427. doi: 10.1038/s41467-018-07815-5.
[h=1]Broad CD8[SUP]+[/SUP] T cell cross-recognition of distinct influenza A strains in humans.[/h] Grant EJ[SUP]1,[/SUP][SUP]2[/SUP], Josephs TM[SUP]2[/SUP], Loh L[SUP]1[/SUP], Clemens EB[SUP]1[/SUP], Sant S[SUP]1[/SUP], Bharadwaj M[SUP]1[/SUP], Chen W[SUP]3[/SUP], Rossjohn J[SUP]2,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Gras S[SUP]6,[/SUP][SUP]7[/SUP], Kedzierska K[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8[SUP]+[/SUP] T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCRαβ) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCRαβ cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8[SUP]+[/SUP] T-cell epitopes, HLA-B*37:01-restricted NP[SUB]338-346[/SUB] (B37-NP[SUB]338[/SUB]) and HLA-A*01:01-restricted NP[SUB]44-52[/SUB] (A1-NP[SUB]44[/SUB]). We find high abundance of cross-reactive TCRαβ clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP[SUB]338[/SUB] complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8[SUP]+[/SUP] T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8[SUP]+[/SUP] T-cell-targeted vaccines could provide protection across different IAV strains.
PMID: 30575715 PMCID: PMC6303473 DOI: 10.1038/s41467-018-07815-5
Free PMC Article
[h=1]Broad CD8[SUP]+[/SUP] T cell cross-recognition of distinct influenza A strains in humans.[/h] Grant EJ[SUP]1,[/SUP][SUP]2[/SUP], Josephs TM[SUP]2[/SUP], Loh L[SUP]1[/SUP], Clemens EB[SUP]1[/SUP], Sant S[SUP]1[/SUP], Bharadwaj M[SUP]1[/SUP], Chen W[SUP]3[/SUP], Rossjohn J[SUP]2,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Gras S[SUP]6,[/SUP][SUP]7[/SUP], Kedzierska K[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8[SUP]+[/SUP] T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCRαβ) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCRαβ cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8[SUP]+[/SUP] T-cell epitopes, HLA-B*37:01-restricted NP[SUB]338-346[/SUB] (B37-NP[SUB]338[/SUB]) and HLA-A*01:01-restricted NP[SUB]44-52[/SUB] (A1-NP[SUB]44[/SUB]). We find high abundance of cross-reactive TCRαβ clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP[SUB]338[/SUB] complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8[SUP]+[/SUP] T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8[SUP]+[/SUP] T-cell-targeted vaccines could provide protection across different IAV strains.
PMID: 30575715 PMCID: PMC6303473 DOI: 10.1038/s41467-018-07815-5
Free PMC Article