IMMUNOLOGY2024™ Conference Recordings-Specificity matters: T cell responses to respiratory viral infections

Video Transcription

Video Summary

The speaker describes efforts to define human T-cell correlates of protection and specificity using sequencing-based approaches. First, in a Wellington flu cohort, pre-season blood samples showed that T-cell measures predicted influenza infection better than antibody measures, with circulating CD4 T follicular helper (TFH) cells being the strongest predictor. TFH responses likely reflect the ability to generate mucosal antibody better than blood antibody levels do.<br /><br />Next, lymph node sampling after flu vaccination revealed that even a standard inactivated influenza vaccine induces strong, long-lived TFH maturation, peaking around 90 days and persisting for months. Reverse epitope discovery showed that many dominant TFH responses target internal viral proteins rather than hemagglutinin, which may explain ineffective imprinting and recall-biased responses.<br /><br />The talk then shifts to SARS-CoV-2, where longitudinal TCR sequencing tracked infection and vaccination responses in human blood. This allowed separation of de novo versus cross-reactive T-cell expansions, identified a protective B15-associated cross-reactive epitope, and showed that non-SARS-CoV-2 memory clones were not globally depleted.<br /><br />Finally, by combining TCR similarity with gene-expression data, the speaker used “Conga” to identify pathogen-specific immune “imprints” across huge public datasets. This approach can classify antigen-specific T-cell states and may help build a sequencing-only map of immune history, protection, and pathology.

Keywords

T-cell correlates of protection

CD4 TFH cells

influenza vaccination

TCR sequencing

SARS-CoV-2 immunity

cross-reactive epitopes

Conga immune imprints