CD4+ T Cells Recognize Conserved Influenza A Epitopes through Shared Patterns of V-Gene Usage and Complementary Biochemical Features

• DOI: 10.1016/j.celrep.2020.107885
• Publication Date: 2020-07-14T14:37:52Z
• Authors: Alexander Greensh...; Meriem Attaf; Bruce J. MacLachlan; Thomas Whalley; Cristina Rius; Aaron Wall; Angharad Lloyd; Hywel Hughes; Kathryn E. Strange; Georgina H. Mason; Andrea J. Schauen...; Sarah L. Hulin-Cu...; James Geary; Yuan Chen; Sarah N. Lauder; Kathryn Smart; Dhanasekaran Vija...; Miguel L. Grau; Mikhail Shugay; Robert Andrews; Garry Dolton; Pierre J. Rizkallah; Awen M. Gallimore; Andrew K. Sewell; Andrew J. Godkin; David K. Cole
• Keywords: Adult; CD4-Positive T-Lymphocytes; Male; QH301-705.5; Amino Acid Motifs; CD4 T cells; Immunoglobulin Variable Region; Receptors, Antigen, T-Cell; Article; Birds; Epitopes; 03 medical and health sciences; 0302 clinical medicine; Animals; Humans; Amino Acid Sequence; Biology (General); Conserved Sequence; Immunodominant Epitopes; HLA-DR1 Antigen; Middle Aged; Complementarity Determining Regions; 3. Good health; peptide epitopes; HLA class II; Germ Cells; pHLA mutlimer; Influenza A virus; Female; T cell receptor; influenza; Peptides

T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated the highly variable receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes using identical or related TCRs expressed on CD8+ cells. Characterization these has extended our understanding molecular mechanisms that govern peptide-HLA. However, few examples exist for CD4+ Here, we investigate to internal proteins influenza A virus correlate with protective immunity. We identify five are commonly recognized cells in HLA-DR1+ subjects and show conservation across strains zoonotic reservoirs. repertoire analysis demonstrates several shared gene usage biases underpinned complementary biochemical features evident a structural comparison. These attractive targets vaccination other therapies.