IMMUNOLOGY2025™ Conference Recordings-Challenging the current paradigms that explain autoimmunity

Challenging the current paradigms that explain autoimmunity - Wayne Yokoyama

Video Transcription

Video Summary

The speaker reflected on growing up in Hawaii and then described two major lines of research on autoimmunity. First, his lab revisited an old, poorly understood mouse virus once called MTV and identified it through modern deep sequencing as murine roseola virus (MRV), a herpesvirus-like agent related to human HHV-6/7. MRV infection in newborn mice caused thymic damage, immune cell loss, and later autoimmune gastritis with broad autoantibody production. The work suggests autoimmunity may arise not only from molecular mimicry, but also from disruption of central tolerance in the thymus.<br /><br />Second, he discussed HLA-B27 and its strong association with ankylosing spondylitis and anterior uveitis. Using single-cell RNA-seq on patient samples and peptide-screening approaches, his team identified expanded T-cell clones with shared receptor features that recognized both bacterial and self peptides presented by disease-associated HLA-B27 subtypes. Structural studies showed how these T-cell receptors can bind cross-reactive peptides similarly. The findings support a refined “arthritogenic peptide” model in which microbial peptides may prime T cells that later attack self tissues such as the eye or joints.

Keywords

autoimmunity

murine roseola virus

thymic damage

central tolerance

HLA-B27

ankylosing spondylitis

anterior uveitis

T-cell cross-reactivity

arthritogenic peptide model