Of identified genetic variants,HLA polymorphisms confer the greatest risk for developing autoimmune diseases, including rheumatoid arthritis (HLA-DRB1∗04). There are strong influences of HLA polymorphisms on cell type-specific gene expression in B cells and monocytes. Their influence on gene expression in CD4+ T cells is not known. We determined transcript and proteins levels of target genes in lymphocyte/monocyte subsets in healthy controls and rheumatoid arthritis subjects as a function of HLA-DRB1∗04 haplotype.We identified gene expression dependent on HLA-DRB1∗04 genotype in CD4+ T cells. NF-κB activity in CD4+ T cells was also dependent on HLA-DRB104 genotype, and blocking HLA-DR inhibited NF-κB activity in CD4+ T cells and normalized gene expression, as did pharmacologic inhibition of NFkB. We conclude that interactions between TCR and MHC class II encoded by HLA-DRB104 create a proinflammatory "hum" altering CD4+ T cell phenotype.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy