Journal article
Differing roles of CD1d2 and CD1d1 proteins in type I natural killer T cell development and function
S Sundararaj, J Zhang, SH Krovi, R Bedel, KD Tuttle, N Veerapen, GS Besra, Y Khandokar, T Praveena, J Le Nours, JL Matsuda, J Rossjohn, L Gapin
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2018
Abstract
MHC class I-like CD1 molecules have evolved to present lipid-based antigens to T cells. Differences in the antigen-binding clefts of the CD1 family members determine the conformation and size of the lipids that are presented, although the factors that shape CD1 diversity remain unclear. In mice, two homologous genes, CD1D1 and CD1D2, encode the CD1d protein, which is essential to the development and function of natural killer T (NKT) cells. However, it remains unclear whether both CD1d isoforms are equivalent in their antigen presentation capacity and functions. Here, we report that CD1d2 molecules are expressed in the thymus of some mouse strains, where they select functional type I NKT cel..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank members of our laboratories for thoughtful discussions and critical comments on the manuscript; Chyung-Ru Wang for the CD1D1D2<SUP>-/-</SUP> mice used in this study; Paul B. Savage and Luc Teyton for the alpha- and ss-psychosine antigens; the National Jewish Health flow cytometry facility, the Mucosal and Vaccine Research Colorado Flow Core, and the University of Colorado flow cytometry shared resource facility for assistance with cell sorting; the Center for Genes, Environment, and Health at National Jewish Health for sequencing; the National Institutes of Health (NIH) core facility for CD1d tetramers; the staff at the Australian Synchrotron for assistance with data collection; and the staff at the Monash Macromolecular crystallization facility. This work was supported by NIH Grants AI121761 and AI124076 (to L.G.); an American Association for Immunologists Careers in Immunology Fellowship (L.G.); Cancer Center Support Grant P30CA046934; the National Health and Medical Research Council; Worldwide Cancer Research Grant 16-1106 (to J.R.); and an Australian Research Council Future Fellowship FT160100074 (to J.L.N.).