Laboratory for Human Immunogenetics

Our laboratory aims to elucidate the genetic control of immune functions and autoimmunity risk. Our recent research focuses on multiple research directions as follows. All of these research directions promise to improve our understanding of the genetic basis of autoimmunity risk.

 

I. Functional genetics

We have been working on functional genetics studies to understand the genetic basis of human autoimmunity (Ishigaki et al. Nat Genet 2017). We recently extended this research direction and started a new CRISPR-based genome editing experiment. We also started projects of single-cell eQTL and multi-modal omics data analyses.

 

II. T cell receptor (TCR) 

Polymorphisms in the HLA genes strongly influence autoimmune disease risk. We recently investigated the influence of HLA alleles on TCR composition at the highly diverse complementarity determining region 3 (CDR3), which confers antigen recognition. We demonstrated unexpectedly powerful HLA-CDR3 associations and provided evidence suggesting that this HLA-CDR3 association promotes autoreactivity to pathogenic epitopes (e.g., citrullinated epitopes in rheumatoid arthritis). Please read our recent manuscript for more details: Ishigaki et al., Nat Genet 2022 (https://www.nature.com/articles/s41588-022-01032-z).

In another recent project, we developed a novel analytic strategy that assesses the TCR characteristics of regulatory T cells (T-reg). We demonstrated that the CDR3 hydrophobicity and the usage of some TCR V genes increase the likelihood that thymic T cells will acquire a T-reg phenotype. Please read our recent manuscript for more details: Lagattuta et al., Nat Immunol 2022 (https://www.nature.com/articles/s41590-022-01129-x).

 

III. Clinical applications