IMPACTing autoimmunity through dual targeting of antigen presenting cells and T cells via inhibitory receptor agonism

Engineered Jurkat Cells for Targeting Prostate-Specific Membrane Antigen on Prostate Cancer Cells by Nanobody-Based Chimeric Antigen Receptor

Background: Recently, modification of T cells with chimeric antigen receptor (CAR) has been an attractive approach for adoptive immunotherapy of cancers. Typically, CARs contain a single-chain variable domain fragment (scFv). Most often, scfvs are derived from a monoclonal antibody of murine origin and may be a trigger for host immune system that leads to the T-cell clearance. Nanobody is a spe...

Dual T cell receptor alpha chain T cells in autoimmunity

Allelic exclusion at the T cell receptor alpha locus TCR-alpha is incomplete, as demonstrated by the presence of a number of T lymphocyte clones carrying two expressed alpha chain products. Such dual alpha chain T cells have been proposed to play a role in autoimmunity, for example, because of a second TCR-alpha beta pair having bypassed negative selection by virtue of low expression. We examin...

The Immunomodulatory Effect of Cyclophosphamide on Regulation of T-Cell Subsets and Antigen Presenting Cells.

Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity

The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic beta-islet cells together with T cells expressing an LCMV-gp-specific T cell receptor to assess the requi...

Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells

Langerhans cells (LCs) are antigen-presenting cells in the epidermis whose roles in antigen-specific immune regulation remain incompletely understood. Desmoglein 3 (Dsg3) is a keratinocyte cell-cell adhesion molecule critical for epidermal integrity and an autoantigen in the autoimmune blistering disease pemphigus. Although antibody-mediated disease mechanisms in pemphigus are extensively chara...