HLA Immunogenetics Section

Overview

The HLA Immunogenetics section studies the influence of immunogenetic variation on risk of human disease, outcome to therapeutic treatment, and vaccination.  These studies include elucidation of the functional basis for the genetic associations identified. 

The human leukocyte antigen (HLA) class I and class II genetic loci are the main subjects of our research. Apart from HLA genetic variation, there are other mechanisms by which HLA influences the immune response.  These include:  

  1. HLA class I interactions with innate immune receptors such as KIR and LILR 
  2. Cell surface expression levels of HLA class I and class II 
  3. Allele-specific variation in HLA dependency on tapasin, a key component involved in loading of antigenic peptides.  

We are also developing innovative approaches to analyze gene-disease associations by combining experimental and computational methods. 

Focus

Genetic effects of immune related genes on disease outcome 

  • Determine alleles, genotypes, and haplotypes of HLA class I and II that are associated with a given disease.  
  • Identify cis or trans genetic variation that affects HLA expression levels and determine the impact of differing expression levels on disease outcomes. 
  • Identify disease associations with natural killer cell receptor genetic variation in combination with relevant HLA binding characteristics. 

Characterize genetic regulation of HLA antigen presentation 

  • Determine HLA allele-specific tapasin dependence for all common HLA alleles. 
  • Investigate HLA class I allele-specific peptide repertoire breadth and affinity of the HLA-peptide complexes. 
  • Determine the impact of members of the peptide loading complex on peptide selection and presentation on the cell surface through generation of cell lines with genetic knockouts of the respective genes using CRISPR technology. 
  • Define the impact of the HLA leader sequence on HLA cell surface expression. 
  • Apply a computational approach tcomprehensively to study HLA allotype-specific peptide repertoires using large mass-spectrometry datasets.

Determine the functional significance of genetic associations identified in the laboratory

  • Define the role of HLA in regulation of natural killer cell functions in disease. 
  • Define the role of HLA class I genotypes on HLA-E function using various molecular biology techniques and in vitro cellular models.