Data from: Validation of a murine proteome-wide phage display library for identification of autoantibody specificities

Autoimmunity is characterized by loss of tolerance to tissue-specific as
well as systemic antigens, resulting in complex autoantibody landscapes.
Here, we introduce and extensively validate the performance
characteristics of a murine proteome-wide library for phage display
immunoprecipitation and sequencing (PhIP-seq), to profile mouse
autoantibodies. This system and library were validated using seven genetic
mouse models across a spectrum of autoreactivity. Mice deficient in
antibody production (Rag2-/- and mMT) were used to model non-specific
peptide enrichments, while cross-reactivity was evaluated using
anti-ovalbumin B cell receptor (BCR)-restricted OB1 mice as a proof of
principle. The PhIP-seq approach was then utilized to interrogate three
distinct autoimmune disease models. First, serum from Lyn-/- IgD+/- mice
with lupus-like disease was used to identify nuclear and apoptotic bleb
reactivities, lending support to the hypothesis that apoptosis is a shared
origin of these antigens. Second, serum from non-obese diabetic (NOD)
mice, a polygenic model of pancreas-specific autoimmunity, enriched
peptides derived from both insulin and predicted pancreatic proteins.
Lastly, Aire-/- mouse sera were used to identify numerous auto-antigens,
many of which were also observed in previous studies of humans with
autoimmune polyendocrinopathy syndrome type 1 (APS1) carrying recessive
mutations in AIRE. Among these were peptides derived from Perilipin-1, a
validated autoimmune biomarker of generalized acquired lipodystrophy in
humans. Autoreactivity to Perilipin-1 correlated with lymphocyte
infiltration in adipose tissue and underscores the approach in revealing
previously unknown specificities. These experiments support the use of
murine proteome-wide PhIP-seq for antigenic profiling and autoantibody
discovery, which may be employed to study a range of immune perturbations
in mouse models of autoimmunity.