Distinguished Lecture von Alicia Sanchez-Mazas: "The intriguing evolution of HLA genes in human populations"

Human leukocyte antigen (HLA) molecules play a key role in our adaptive immunity by presenting pathogen-derived peptides to T lymphocytes, what triggers an immune response and protects individuals against diseases. HLA genes are highly variable in human populations, an observation that is mainly considered as a consequence of heterozygous advantage in pathogen-rich environments. In addition to this overall effect, a number of HLA alleles have been proposed as susceptibility or protective factors to infectious diseases (besides autoimmune diseases and cancers), some of which are highly prevalent in specific geographic regions. In this talk, we present the results of our most recent studies on HLA variation in humans. We show that the heterogeneous distribution of HLA alleles across populations can be explained by both demographic events linked to the history of human migrations across the continents (e.g. the colonisation of East Asia through two routes of migrations along both sides of the Himalayas) and natural selection due to the adaptation of populations to distinct environments (e.g. a protective effect of HLA-B alleles to malaria in sub-Saharan Africa). In addition, we demonstrate that despite their heterogeneous levels of diversity at individual HLA loci (e.g. very low in some small populations like native Taiwanese or Americans), all populations exhibit a similar potential to present a large variety of peptides thanks to the involvement of several HLA genes, a model that we have called joint divergent asymmetric selection. Our current research uses high-throughput sequencing techniques to decipher more in depth the molecular diversity of HLA genes within and across populations in order to better understand the mechanisms that drove the evolution of this fascinating genomic region.