tetano
Editor, Senior Moderator
Cell Rep
. 2020 Jul 14;32(2):107885.
doi: 10.1016/j.celrep.2020.107885.
CD4 [SUP]+[/SUP] T Cells Recognize Conserved Influenza A Epitopes through Shared Patterns of V-Gene Usage and Complementary Biochemical Features
Alexander Greenshields-Watson[SUP] 1 [/SUP], Meriem Attaf[SUP] 1 [/SUP], Bruce J MacLachlan[SUP] 2 [/SUP], Thomas Whalley[SUP] 1 [/SUP], Cristina Rius[SUP] 1 [/SUP], Aaron Wall[SUP] 1 [/SUP], Angharad Lloyd[SUP] 1 [/SUP], Hywel Hughes[SUP] 1 [/SUP], Kathryn E Strange[SUP] 1 [/SUP], Georgina H Mason[SUP] 1 [/SUP], Andrea J Schauenburg[SUP] 1 [/SUP], Sarah L Hulin-Curtis[SUP] 1 [/SUP], James Geary[SUP] 1 [/SUP], Yuan Chen[SUP] 1 [/SUP], Sarah N Lauder[SUP] 1 [/SUP], Kathryn Smart[SUP] 1 [/SUP], Dhanasekaran Vijaykrishna[SUP] 3 [/SUP], Miguel L Grau[SUP] 3 [/SUP], Mikhail Shugay[SUP] 4 [/SUP], Robert Andrews[SUP] 1 [/SUP], Garry Dolton[SUP] 1 [/SUP], Pierre J Rizkallah[SUP] 1 [/SUP], Awen M Gallimore[SUP] 1 [/SUP], Andrew K Sewell[SUP] 1 [/SUP], Andrew J Godkin[SUP] 5 [/SUP], David K Cole[SUP] 6 [/SUP]
Affiliations
Abstract
T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8[SUP]+[/SUP] T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4[SUP]+[/SUP] T cells. Here, we investigate CD4[SUP]+[/SUP] T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4[SUP]+[/SUP] T cells in five HLA-DR1[SUP]+[/SUP] subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies.
Keywords: CD4 T cells; HLA class II; T cell receptor; X-ray crystallography; biochemistry; clonotyping; immunology; influenza; pHLA mutlimer; peptide epitopes.
. 2020 Jul 14;32(2):107885.
doi: 10.1016/j.celrep.2020.107885.
CD4 [SUP]+[/SUP] T Cells Recognize Conserved Influenza A Epitopes through Shared Patterns of V-Gene Usage and Complementary Biochemical Features
Alexander Greenshields-Watson[SUP] 1 [/SUP], Meriem Attaf[SUP] 1 [/SUP], Bruce J MacLachlan[SUP] 2 [/SUP], Thomas Whalley[SUP] 1 [/SUP], Cristina Rius[SUP] 1 [/SUP], Aaron Wall[SUP] 1 [/SUP], Angharad Lloyd[SUP] 1 [/SUP], Hywel Hughes[SUP] 1 [/SUP], Kathryn E Strange[SUP] 1 [/SUP], Georgina H Mason[SUP] 1 [/SUP], Andrea J Schauenburg[SUP] 1 [/SUP], Sarah L Hulin-Curtis[SUP] 1 [/SUP], James Geary[SUP] 1 [/SUP], Yuan Chen[SUP] 1 [/SUP], Sarah N Lauder[SUP] 1 [/SUP], Kathryn Smart[SUP] 1 [/SUP], Dhanasekaran Vijaykrishna[SUP] 3 [/SUP], Miguel L Grau[SUP] 3 [/SUP], Mikhail Shugay[SUP] 4 [/SUP], Robert Andrews[SUP] 1 [/SUP], Garry Dolton[SUP] 1 [/SUP], Pierre J Rizkallah[SUP] 1 [/SUP], Awen M Gallimore[SUP] 1 [/SUP], Andrew K Sewell[SUP] 1 [/SUP], Andrew J Godkin[SUP] 5 [/SUP], David K Cole[SUP] 6 [/SUP]
Affiliations
- PMID: 32668259
- DOI: 10.1016/j.celrep.2020.107885
Abstract
T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8[SUP]+[/SUP] T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4[SUP]+[/SUP] T cells. Here, we investigate CD4[SUP]+[/SUP] T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4[SUP]+[/SUP] T cells in five HLA-DR1[SUP]+[/SUP] subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies.
Keywords: CD4 T cells; HLA class II; T cell receptor; X-ray crystallography; biochemistry; clonotyping; immunology; influenza; pHLA mutlimer; peptide epitopes.