Integrated Methodology from Synthesis to <i>in Vivo</i> Study that Identifies Nanostructure Shape “Hot Spots” in T Cell Receptor Repertoire

A new integrated tunable microfluidic particle synthesis and shape population analysis workflow allows us to study the immunological readouts for even highly complex shaped nanoparticles. Using this approach, we demonstrate that some gold nanoparticles, when injected parenterally, are taken up by axillary and brachial lymph nodes. We then show that specific nanoparticle shapes influence the primary structure of the T cell receptor, inducing changes in hypervariable complementary-determining regions (CDRs) and increasing the clonal diversity of the T cell receptor repertoires. These same particles were previously found to modify cellular epigenomes and elevate the level of autoantibodies. Our results are consistent with other emerging reports that precisely controlled nanoarchitectural features are recognized and captured in multiple tiers of biology, with potential implications for vaccine adjuvant design. Our conclusions may also be relevant to an extensive legacy of poorly understood epidemiological studies, suggesting links between some pollutant particulates and complex forms of immune dysregulation and autoimmune diseases.