Molecular Discovery, and Flow Cytometry Core Facility for their
technical support.Funding:This study is partially funded by
the United Technologies Corporation Endowment at Yale,
Boehringer Ingelheim Inc, and NIH P30 CA016359. M.D.V. is
supported by a Physician-Scientist Career Development Award
from the Dermatology Foundation, a Dermatology Fellow
Award from the Melanoma Research Alliance, and KL2 TR001862
from the National Center for Advancing Translational Sciences
(NCATS) through Yale Center for Clinical Investigation.Author
contributions:L.Z. and L.C. conceived and designed the project.
L.Z. performed most of the experiments in this study. X.H.
assisted with antibody generation, ELISA, IVIS imaging, and in vivo
assays. S.Y., L.J., G.Z., and J.W. assisted with the receptor array.
Y.Z. assisted with antibody generation and in vivo experimental
design. J.K. and S.W. assisted with the in vivo functional
characterization of the 9B12 mAb and edited the manuscript.
W.Y. and B.H. assisted with the characterization ofPilraknockout
mice. M.D.V. assisted with the tissue redistribution experiments
and edited the manuscript. X.C. and E.Q. assisted with the
antibody Fab fragment and protein binding assays. Z.T. sorted
cells. J.P. provided technical support. L.Z. and L.C. analyzed
the data and wrote the manuscript.Competing interests:A
patent application has been filed based on data in this manuscript.
In the past year, L.C. has been a scientific founder, consultant, and
board member for NextCure, Junshi, Normunity, Tayu, Zai Lab,
Tpioneer, Vcanbio, and GenomiCare and has sponsored research
funds from NextCure, Normunity, and DynamiCure. The other
authors have no competing interests.Data and materials
availability:All data are available in the main text and
supplementary materials. All plasmids, antibodies, and mice are
available through a material transfer agreement with Yale
University by contacting the corresponding author.License
information:Copyright © 2022 the authors, some rights reserved;
exclusive licensee American Association for the Advancementof Science. No claim to original US government works.
https://www.science.org/about/science-licenses-journal-article-reuseSUPPLEMENTARY MATERIALS
science.org/doi/10.1126/science.aaz8658
Materials and Methods
Figs. S1 to S32
Table S1
References ( 30 – 36 )
MDAR Reproducibility Checklist
View/request a protocol for this paper fromBio-protocol.Submitted 15 October 2019; resubmitted 10 November 2020
Accepted 25 April 2022
10.1126/science.aaz8658Zhenget al., Science 376 , 996–1001 (2022) 27 May 2022 6of6
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