The size of micro-crystalline tyrosine (MCT®) influences its recognition and uptake by THP-1 macrophages in vitro

Abstract

The physicochemical hallmarks of particulate immunopotentiators play a pivotal role with regards to their adjuvanticity in vivo. These properties have not been fully characterised in the case of MCT®, an amino acid-based adjuvant used as an alternative to aluminium salts in subcutaneous allergy immunotherapy (SCIT). This study presents a full characterisation of MCT® and in a preliminary capacity reveals how parameters, specifically particle size, might influence the recognition of MCT® by antigen presenting cells (APCs) in vitro. Light microscopic analysis demonstrated that MCT® was composed of highly crystalline needles, the majority of which exceeded 10 μm in length under physiological conditions (median size – 20.8 μm). While the substantial length of crystals presented a significant barrier to cellular recognition and uptake, isolated incidences of perpendicular recognition were observed owing to the smaller comparative width of crystallites (median size – 2.8 μm). This appeared to allow a small proportion of material to be ingested both fully and partially by THP-1 macrophages, although further studies are required to unequivocally confirm this observation. Preferential recognition of needle tips also favoured the direct presentation of antigen to immune cells as proteinaceous adsorption appeared to be isolated to these regions. Furthermore, the data herein provide valuable insights into the mechanisms surrounding how this adjuvant potentiates an immunological response following administration.