The development of immunological tolerance to orally fed antigens depends o
n the sampling, processing and transportation events followed in the intest
inal epithelium. We present here a description of a "tolerosome": a supra-m
olecular, exosome-like structure assembled in and released from the small i
ntestinal epithelial cell. The tolerosome is a approximate to 40 nm large v
esicular structure that carries MHC class II (MHC II) with bound antigenic
peptides sampled from the gut lumen. Tolerosomes isolated from serum shortl
y after antigen feeding or from an in vitro pulsed intestinal epithelial ce
ll line are fully capable of inducing antigen specific tolerance in naive r
ecipient animals. Purified tolerosomes represent a structure by which fed a
ntigens can be efficiently presented to the immune system. Removal of the t
olerosomes from serum by ultracentrifugation or absorption of MHC II result
s in abrogated tolerance development.