Pathogen Adaptation of HLA Alleles and Its Correlation with Autoimmune Diseases in the Han Chinese

Abstract

Human leukocyte antigen (HLA) genes play a crucial role in the adaptation of human populations to the dynamic pathogenic environment. Despite their significance, investigating the pathogen-driven evolution of HLAs and its implications for autoimmune diseases presents considerable challenges. Here, we genotyped over 20 HLA genes at 3-field resolution in 8278 individuals from diverse ethnic backgrounds, including 4013 unrelated Han Chinese individuals. We focused on the adaptation of HLAs in the Han Chinese population by analyzing their binding affinity for various pathogens, and explored the potential correlations between pathogen adaptation and autoimmune diseases. Our findings reveal that specific HLA alleles like HLA-DRB1*07:01 and HLA-DQB1*06:01 confer strong pathogen adaptability at the sequence level, notably for Corynebacterium diphtheriae and Bordetella pertussis. Additionally, alleles like HLA-C*03:02 demonstrate adaptive selection against pathogens like Mycobacterium tuberculosis and coronavirus at the gene expression level. Simultaneously, the aforementioned HLA alleles are closely related to some autoimmune diseases such as multiple sclerosis. These exploratory discoveries shed light on the intricate coevolutionary relationships between pathogen adaptation and autoimmune diseases in the human population. These efforts led to an HLA database at http://bigdata.ibp.ac.cn/HLAtyping, aiding searches for HLA allele frequencies across populations. Keywords: HLA genotype, Han Chinese, HLA–peptide binding, Pathogen adaptation, Autoimmune disease