Project description:Several HLA allelic variants have been associated with protection from, or susceptibility to infectious and autoimmune diseases. Here, we examined whether specific HLA alleles would be associated with different Mtb infection outcomes. We found that DQA1*03:01, DPB1*04:02, and DRB4*01:01 were signficantly more frequent in inividuals with active TB (susceptibility alleles). Furthermore, individuals who express any of the three susceptibility alleles were associated with lower magnitude of responses against Mtb antigens. We investigated the gene expression changes induced in PBMCs by Mtb lysate and a peptide pool (MTB300) in individuals with or without expression of the susceptibility alleles.
Project description:HLA DRB1*15:01 is overrepresentated in Parkinson's disease patients and binds with high affinity to the ⍺-synuclein peptide, 32-46. Immunization of humanized mice expressing HLA DRB1*15:01 with ⍺-syn32-46 induces enteric phenotypes similar to those of prodromal Parkinson's disease. We collected the ileum from HLA mice immunized with either Complete Freund's Adjuvant (CFA) with ⍺-syn32-46 or CFA alone, and sequenced the tissue with bulk RNA sequencing at 21 days post immunization to determine changes in gene expression.
Project description:HLA DRB1*15:01 is overrepresentated in Parkinson's disease patients and binds with high affinity to the ⍺-synuclein peptide, 32-46. Immunization of humanized mice expressing HLA DRB1*15:01 with ⍺-syn32-46 induces enteric phenotypes similar to those of prodromal Parkinson's disease. We collected the small intestines from HLA mice immunized with either Complete Freund's Adjuvant (CFA) with ⍺-syn32-46 or CFA alone, sorted the CD45+ immune cells, then performed single-cell RNA sequencing to evaluate gene expression at single cell resolution.
