Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses

作者：Hammer Christian^*; Begemann Martin; McLaren Paul J; Bartha Istvan; Michel Angelika; Klose Beate; Schmitt Corinna; Waterboer Tim; Pawlita Michael; Schulz Thomas F; Ehrenreich Hannelore; Fellay Jacques

来源：American Journal of Human Genetics, 2015, 97(5): 738-743.

DOI：10.1016/j.ajhg.2015.09.008

The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed in the major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr virus, JC polyomavirus, and Merkel cell polyomavirus. Using local imputation and fine mapping, we identified specific amino acid residues in human leucocyte antigen (HLA) class II proteins as the most probable causal variants underlying these association signals. Common HLA-DR beta 1 haplotypes showed virus-specific patterns of humoral-response regulation. We observed an overlap between variants affecting the humoral response to influenza A and EBV and variants previously associated with autoimmune diseases related to these viruses. The results of this study emphasize the central and pathogen-specific role of HLA class II variation in the modulation of humoral immune response to viral antigens in humans.

• 出版日期2015-11-5