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

## TL;DR

This paper introduces a new method to study how the shape of gold nanoparticles affects the T cell receptor repertoire and immune responses in vivo.

## Contribution

The novel contribution is an integrated workflow combining microfluidic synthesis and immunological analysis to identify nanoparticle shape effects on T cell receptors.

## Key findings

- Certain gold nanoparticle shapes are taken up by axillary and brachial lymph nodes after parenteral injection.
- Specific nanoparticle shapes alter T cell receptor structures and increase clonal diversity in CDR regions.
- These particles previously modified cellular epigenomes and increased autoantibody levels.

## Abstract

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.