Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells

The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals

Perspectives on Teaching Foreign and International Legal Research

This article discusses various models for teaching international and foreign legal research. In some law schools, international and foreign legal research is a semester-long course. In other law schools, international and foreign legal research is a component of an advanced legal research seminar or an international law course. Stefanie Weigmann presents an overview of teaching international legal research and describes her experience teaching in various formats. Katherine Topulos outlines some of the resources that are helpful for those who want to begin teaching foreign and international legal research. Jean Davis and Victoria Szymczak discuss teaching techniques and class activities for a semester-long course