Fourie, A. | bioRxiv Science

bioRxiv2025

A transgenic mouse allows to capture the HLA-C*06:02 immunopeptidome in a model of psoriasis

Psoriasis vulgaris is a T cell-mediated autoimmune skin condition affecting around one in fifty people worldwide. Whilst advanced immunomodulatory therapeutic options have become available in recent years, ongoing disease suppression is still required with no curative treatment available to date. The human leukocyte antigen class I allele HLA-C*06:02 is the main genetic risk determinant of psoriasis. Its function is to present peptide antigens to CD8+ T cells and natural killer cells which in turn elicit and perpetuate the immune response, yet little is known about ligands presented by HLA-C*06:02. To gain an understanding which HLA-C*06:02-restricted peptides are presented by epidermal cell populations and might be initiators of the autoimmune response in psoriasis, we have conducted an in depth immunopeptidomics analysis of HLA-C*06:02+ keratinocyte and melanocyte cell lines. Furthermore, we introduce a HLA-C*06:02 transgenic mouse which, in conjunction with the imiquimod model of psoriasis, allowed us to assess the ex vivo immunopeptidome of HLA-C*06:02 in psoriasiform skin. Overall, we detected 20,812 high confidence HLA-C*06:02 bound peptide ligands. Thus, we present a comprehensive coverage HLA-C in vitro immunopeptidomics dataset and the first HLA-C*06:02 ex vivo dataset of psoriasis-relevant peptide antigens that may inform the development of antigen-specific, novel curative therapeutic approaches in psoriasis.

immunology↗

bioRxiv2024

Bacterial family-specific enrichment and functions of secretion systems in the rhizosphere

The plant rhizosphere is a highly selective environment where bacteria have developed traits to establish themselves or outcompete other microbes. These traits include bacterial secretion systems (SSs) that range from Type I (T1SS) to Type IX (T9SS) and can play diverse roles. The best known functions are to secrete various proteins or other compounds into the extracellular space or into neighbouring cells, including toxins to attack other microbes or effectors to suppress plant host immune responses. Here, we aimed to determine which bacterial SSs were associated with the plant rhizosphere. We utilised paired metagenomic datasets of rhizosphere and bulk soil samples from five different plant species grown in a wide variety of soil types, amounting to ten different studies. The T3SS and T6SS were generally enriched in the rhizosphere, as observed in studies of individual plant-associated genera. We also identified additional SSs that have received less attention thus far, such as the T2SS, T5SS and Bacteroidetes-specific T6SSiii and T9SS. The predicted secreted proteins of some of these systems (T3SS, T5SS and T6SS) could be linked to functions such as toxin secretion, adhesion to the host and facilitation of plant-host interactions (such as root penetration). The most prominent bacterial taxa with rhizosphere- or soil-enriched SSs included Xanthomonadaceae, Oxalobacteraceae, Comamonadaceae, Caulobacteraceae, and Chitinophagaceae, broadening the scope of known plant-associated taxa that use these systems. We anticipate that the SSs and taxa identified in this study may be utilised for the optimisation of bioinoculants to improve plant productivity.

microbiology↗