HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis.

The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4 T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells.

deletion results in depletion of the transcription factor and a specific loss of parvalbumin cortical interneurons.

Neurofibromatosis 1 (NF1) is caused by mutations in the gene, which encodes the protein, neurofibromin, an inhibitor of Ras activity. Cortical GABAergic interneurons (CINs) are implicated in NF1 pathology, but the cellular and molecular changes to CINs are unknown. We deleted mouse from the medial ganglionic eminence, which gives rise to both oligodendrocytes and CINs that express somatostatin and parvalbumin.

Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death.

Galectin-1 kills immature thymocytes and activated peripheral T cells by binding to glycans on T cell glycoproteins including CD7, CD45, and CD43. Although roles for CD7 and CD45 in regulating galectin-1-induced death have been described, the requirement for CD43 remains unknown. We describe a novel role for CD43 in galectin-1-induced death, and the effects of O-glycan modification on galectin-1 binding to CD43.

Real-time quantification of microRNAs by stem-loop RT-PCR.

A novel microRNA (miRNA) quantification method has been developed using stem-loop RT followed by TaqMan PCR analysis. Stem-loop RT primers are better than conventional ones in terms of RT efficiency and specificity. TaqMan miRNA assays are specific for mature miRNAs and discriminate among related miRNAs that differ by as little as one nucleotide.

Potential role for mitogen-activated protein kinase phosphatase-1 in the development of atherosclerotic lesions in mouse models.

Objective: Mitogen-activated protein kinase phosphatase-1 (MKP-1) is one of several oxidized-l-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC)-induced genes identified in human aortic endothelial cells (HAEC). We previously reported that MKP-1 activity is required for Ox-PAPC-mediated endothelial/monocyte interactions; however, an in vivo role of MKP-1 in atherogenesis has not been investigated.

Methods And Results: We now report that MKP-1 protein is expressed in the atherosclerotic lesions of mice.

Repetitive, noninvasive imaging of cyclooxygenase-2 gene expression in living mice.

The cyclooxygenase-2 (COX-2) gene plays a role in a wide variety of normal physiologic pathways and is a major target of pharmacologic intervention in a large number of pathophysiologic contexts, including pain, fever, inflammation, and cancer. Expression of the COX-2 gene is induced in a wide range of cells, in response to an ever-increasing number of stimuli. The regulation of the COX-2 gene has been the subject of extensive study, using traditional transfection techniques with reporter gene constructs.