Hesham ElAbd, PhD

Human leukocyte antigen (HLA) genes represent some of the strongest genetic risk factors for immune-mediated inflammatory diseases, yet the mechanisms linking HLA variation to disease remain poorly understood. Because HLA molecules shape adaptive immune responses through antigen presentation, disease-associated alleles may provide an entry point for identifying the antigens and immune responses that drive disease.

In this talk, I will present a framework for moving from HLA genetic associations toward antigen-specific mechanisms. I will discuss how population-scale T-cell receptor sequencing and statistical analyses can identify clonotypes associated with HLA alleles, antigen exposure, and disease, thereby linking genetic association to adaptive immune responses.

Using examples from inflammatory bowel disease and primary sclerosing cholangitis, I will show how immune-repertoire analysis can be integrated with high-throughput antigen-discovery approaches, including phage immunoprecipitation sequencing, to characterize responses to microbial and viral antigens.

Finally, I will discuss what classes of antigens may underlie immune-mediated inflammatory diseases and how identifying disease-relevant antigenic drivers could advance mechanistic understanding, patient stratification, and the development of antigen-directed therapeutic strategies.