Nanobody-induced perturbation of LFA-1/L-plastin phosphorylation impairs MTOC docking, immune synapse formation and T cell activation

The T cell integrin receptor LFA-1 orchestrates adhesion between T cells and antigen-presenting cells (APCs), resulting in formation of a contact zone known as the immune synapse (IS) which is supported by the cytoskeleton. L-plastin is a leukocyte-specific actin bundling protein that rapidly redistributes to the immune synapse following T cell–APC engagement. We used single domain antibodies (nanobodies, derived from camelid heavy-chain only antibodies) directed against functional and structural modules of L-plastin to investigate its contribution to formation of an immune synapse between Raji cells and human peripheral blood mononuclear cells or Jurkat T cells. Nanobodies that interact either with the EF hands or the actin binding domains of L-plastin both trapped L-plastin in an inactive conformation, causing perturbation of IS formation, MTOC docking towards the plasma membrane, T cell proliferation and IL-2 secretion. Both nanobodies delayed Ser⁵ phosphorylation of L-plastin which is required for enhanced bundling activity. Moreover, one nanobody delayed LFA-1 phosphorylation, reduced the association between LFA-1 and L-plastin and prevented LFA-1 enrichment at the IS. Our findings reveal subtle mechanistic details that are difficult to attain by conventional means and show that L-plastin contributes to immune synapse formation at distinct echelons.     

Structures and strategies in ancient Greek and Roman technical writing: An Introduction

Most of our knowledge of Greek and Roman scientific practice and its place in ancient culture is derived from our study of ancient texts. In the last few decades, this written evidence—ancient technical or specialist literature—has begun to be studied using tools of literary analysis to help answer questions about, for instance, how these works were composed, their authors’ intentions and the expectations of their readers.This introduction to Structures and strategies in ancient Greek and Roman technical writing provides an overview of recent scholarship in the area, and the difficulty in pinning down what ‘technical/specialist literature’ might mean in an ancient context, since Greek and Roman authors communicated scientific knowledge using a wide variety of styles and forms of text (e.g. poetry, dialogues, letters).An outline of the three sections is provided: Form as a mirror of method, in which Sabine Föllinger and Alexander Mueller explore ways in which the structures of texts by Aristotle and Plutarch may reflect methodological concerns; Authors and their implied readers, with contributions by Oliver Stoll, David Creese, Boris Dunsch and Paula Olmos, which examines what ancient texts can tell us about the place of technical knowledge in antiquity; Science and the uses of poetry, with articles by Jochen Althoff, Michael Coxhead and Laurence Totelin, and a new English translation of the Aetna poem by Harry Hine, which explores the (to us) unexpected roles of poetry in ancient scientific culture.