HLA-DO promotes Treg differentiation by altering antigen presentation
نویسندگان
چکیده
Abstract HLA-DO in human (H2-O mice) (DO) is a highly conserved non-classical MHC class II accessory molecule. Unlike the main Class peptide editor HLA-DM, expression of DO restricted to thymic medulla, B cells and certain dendritic cell subsets. forms stable complex with HLA-DM requires DM for trafficking MIIC. Using biochemical experiments, our lab has previously discovered that differential effects on editing peptides different sequences. enhances binding DM-resistant peptides, reduces DM-sensitive HLA-DR1 molecules. Changes quantities either could therefore lead alterations both negative selection, peripheral activation CD4 T cells. single-cell RNA-sequencing (scRNA-seq) from unimmunized knock-out (KO) mice we found an increased frequency “activated” cells, support model. This corresponds decrease “naïve” scRNA-seq FACs analysis. Interestingly, analysis confirmed previous findings elevated regulatory (Treg) levels DO-KO mice. Genetic showed Tregs also have more activated phenotype. These suggests absence generates stimulatory vivo cellular environment likely due altered antigen presentation. Research supported by grants NIH (R01 AI130210, R01 AI121174 R37 AI060040)
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.221.15