Studying how genetic variation affects our B and T cell responses 

Why do some people develop more effective immune responses to infections than others, and what mechanisms drive autoimmune diseases? As a Wallenberg Scholar, Gunilla Karlsson Hedestam will be studying the human immune system with a focus on B och T cell receptors.

B and T lymphocytes are characterised by receptors that recognise foreign structures, antigens, that we are exposed to through infections and vaccinations. The receptors are encoded by approximately 350 genes that exhibit a high degree of variation between persons, which influences how the B and T cells react.

In some cases, the immune system targets the body’s own tissues resulting in autoimmune diseases. We know that genetic factors play roles in the development of such diseases, but many disease susceptibility gene variants remain to be identified.

Gunilla Karlsson Hedestam and her research group have developed new techniques of typing – or classifying – gene variants that encode B and T-cell antigen receptors. The genes are found in regions of our DNA that are so complex that they have not been studied in detail before. 

“Thanks to our new techniques, it’s now possible to sequence thousands of persons simultaneously and study how germline-encoded variations in B and T-cell receptor genes affect the immune system and our health,” says Professor Karlsson Hedestam. 

In the first part of the project, they will interrogate why some people develop more effective immune responses to infections like influenza. In part two, they plan to examine whether variations in the B and T-cell antigen receptor genes influence the risk of developing an autoimmune disease. 

Objectives of the research are to identify gene variants that are protective against certain infections and those that increase the risk of developing autoimmune diseases. 

“We hope that the results can be used to design vaccines that provide broader protection in the population,” says Professor Karlsson Hedestam. “We also hope that they can be used to identify people at risk of autoimmune diseases to facilitate the development of better diagnostics and targeted therapies.”