IMMUNOLOGY2026™-Surprising Insights on Human Immunology from the Study of Monogenic Inborn Errors of Immunity, Sponsored by the Clin. Immunol. Soc. (CIS)

Surprising Insights on Human Immunology from the Study of Monogenic Inborn Errors of Immunity, Sponsored by the Clin. Immunol. Soc. (CIS)

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Video Summary

Dr. Wayne Yokoyama, a leading immunologist known for NK cell research, delivers a lecture challenging the common “molecular mimicry” paradigm of autoimmunity, where pathogen-specific B or T cells are thought to cross-react with self. He presents two lines of work.<br /><br />First, his group revived study of an obscure mouse pathogen originally called murine thymic virus by obtaining an outbreak isolate and sequencing it. They identified it as a herpesvirus closely related to human HHV6/7 and renamed it murine roseola virus (MRV). Neonatal MRV infection causes runting, thymic atrophy, and transient loss of peripheral T cells; weeks later immune cell numbers recover. However, adult mice previously infected as neonates frequently develop autoimmune gastritis and broad autoantibody production. Single-cell RNA-seq showed replicating virus infects not only thymocytes but also thymic antigen-presenting cells (medullary thymic epithelial cells and dendritic cells), suggesting disrupted central tolerance allows autoreactive T cells to escape.<br /><br />Second, he revisits HLA-B27–associated disease (ankylosing spondylitis and anterior uveitis). Using single-cell RNA-seq from eye fluid and joint samples, his team and collaborators found clonally expanded T cells with a shared TCR pairing (TRBV9 with TRAV21). A yeast-display peptide screen and structural studies showed these TCRs recognize both bacterial and self peptides presented by disease-associated HLA-B27 subtypes, supporting an “arthritogenic peptide” mechanism potentially linked to gut inflammation/dysbiosis and offering new therapeutic targets.

Meta Tag

Date April 18, 2026 8:00 AM - 9:30 AM

Room 104C

Session Surprising Insights on Human Immunology from the Study of Monogenic Inborn Errors of Immunity, Sponsored by the Clin. Immunol. Soc. (CIS)

Speaker Janet Markle

Track Human/translational immunology

Year 2026

Keywords

Surprising Insights on Human Immunology from the Study of Monogenic Inborn Errors of Immunity, Sponsored by the Clin. Immunol. Soc. (CIS)

Janet Markle

April 18, 2026 8:00 AM - 9:30 AM

104C

Human/translational immunology

2026

Wayne Yokoyama

natural killer (NK) cells

murine roseola virus (MRV)

neonatal herpesvirus infection

thymic atrophy and central tolerance

autoimmune gastritis

single-cell RNA sequencing

HLA-B27 ankylosing spondylitis

arthritogenic peptide and TCR TRBV9-TRAV21