Poster Presentation Australasian Society for Dermatology Research Annual Scientific Meeting 2024

Investigating the Link Between HLA-C*06:02 and Bacterial Infection in Psoriasis (#63)

Runqiu Song 1 , Mariam Bafit 1 , Kirsteen M. Tullett 1 , Peck Szee Tan 1 , Mireille H. Lahoud 1 , Meredith O'Keeffe 1 , Anthony W. Purcell 1 , Asolina Braun 1
  1. Department of biochemistry and molecular biology, Monash University, Melbourne, Victoria, Australia

The multi-factorial cause of psoriasis onset adds to the complexity of disease aetiology. Psoriasis is thought to be triggered by both, globally prevalent Streptococcus pyogenes (S. pyogenes) throat infections and the carriage of the main genetic risk allele HLA-C*06:02, a member of human leukocyte antigen (HLA) class I proteins which present peptide antigens to immune cells. Evidence of past streptococcal infections can be detected more frequently in HLA-C*06:02+ than in HLA-C*06:02- psoriatic patients. However, although a strong link between these two risk factors has been consistently suggested through correlation, it has not yet been experimentally verified. We believe that the HLA-C*06:02-initiated immune response against S. pyogenes can cause misguided recruitment of autoreactive immune cells to the skin where they cause psoriasis, and we sought to determine which S. pyogenes-derived peptides are presented by HLA-C*06:02. A particular subtype of antigen-presenting cells called cDC1 (type 1 conventional dendritic cells) are proficient in the cross-presentation of HLA class I peptide antigens. Using our novel HLA-C*06:02 transgenic mice, we optimized a bone marrow isolation method with Flt3 expansion to increase the yield of cDC1. The Flt3-ligand-derived cDC1 were exposed to heat-inactivated S. pyogenes and HLA-C*06:02-bound peptides were isolated. Using tandem mass spectrometry (LC-MS/MS), we identified 52 S. pyogenes-derived peptides, among which eight were predicted as HLA-C*06:02 ligands and four of these predicted ligands showed high similarity with human peptides. Such antigen candidates may provide a molecular link between the genetic and environmental risk factors of psoriasis. A better understanding of streptococcal and other environmental antigens could pave the way for preventing S. pyogenes infections and psoriasis.