The study also identified over 300 previously unknown gene variants, which wereshown to be present in different frequencies in different population groups.
The human immune system has evolved over many thousands of years in populations living in widely differing environments, resulting in localised adaptation of the antibody genes to the predominant diseases, explains Martin Corcoran , researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
“The ability to map these genes in large groups of individuals will provide new knowledge about how immune gene differences affect our physiology in a range of conditions, ranging from infections and autoimmune diseases to cancer and, critically, provide a mechanism to read the immunological history of our species encoded within our DNA,” he says.
Some antibody responses may not occur
In the second study, the researchers, in collaboration with the Scripps Research Institute in the USA, investigated how genetic differences affect the immune response to the influenza virus. Using a new technique called ISCAPE, also developed at the Karlsson Hedestam laboratory, they were able to analyse individual B cells from four healthy adults and identify which antibody genes are used to produce neutralising antibodies against the surface hemagglutinin (HA) protein.
The analysis again showed large differences between individuals and identified a common genetic variant that was found to affect the ability to form a certain class of neutralising antibodies against the part of HA that the virus uses to bind to our cells. Importantly the researchers showed that many of the neutralising antibodies required the use of IGHD genes that are absent in many individuals, especially antibodies that bind to the more stable stem region of HA – a structure that is important in the development of broad influenza vaccines.
“We see that certain types of antibody responses are possible only in people with specific gene variants. This shows how important it is to take genetic diversity into account when designing vaccines that will work globally,” says Gunilla Karlsson Hedestam.
Both studies were funded by grants from the Swedish Research Council, the European Research Council (ERC), the Knut and Alice Wallenberg Foundation. Alexandra Fischer, PhD student at Karolinska Institutet, and Martin Corcoran are co-first authors of the second study, which was also funded by grants from SciLifeLab and the US National Institutes of Health. Martin Corcoran and Gunilla Karlsson Hedestam are founders of ImmuneDiscover Sweden AB and have filed patent applications for the technologies used in the studies.
Publications
Ultra-high-throughput IGH genotyping of 25 global populations reveals population-biased allelic diversity and homozygous V and D gene deletions , Martin Corcoran, Sanjana Narang, Mateusz Kaduk, Mark Chernyshev, Anna Färnert, Christopher Sundling, Gunilla B. Karlsson Hedestam, Immunity, online 16 March 2026, doi: 10.1016/j.immuni.2026.01.026.
Genetically diverse influenza antibodies highlight the role of IG germline gene variation and informs population-comprehensive vaccine strategies , Alexandra Fischer, Martin Corcoran, Philip Brouwer, Mark Chernyshev, Rebecca Gillespie, Andrea Nicoletti, Johannes Loeffler, Ioannis Zygouras, Pradeepa Pushparaj, Alesandra Rodriguez, Sanjana Narang, Marit van Gils, Xaquin Castro Dopico, Masaru Kanekiyo, Andrew Ward, Julianna Han, Gunilla B. Karlsson Hedestam, Immunity, online 26 March 2026, doi: 10.1016/j.immuni.2026.03.002.
