A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation.

"the starting structures have been taken from the corresponding wt lck x-ray ones (pdb id: 3lck for the active state; 2pl0 for the inactive state) and the p440s variant has been included by molecular modeling by means of chimera ucsf software. unprocessed images of immunoblots and fcs files from mass cytometry and flow cytometry experiments are openly available in mendeley data at doi: 10 17632/n8658z8fg5 2 ( lui and hsieh 2023 )."

"Disclosures: M. Hoenig reported personal fees from Octapharma (scientific board) outside the submitted work. J. Capera reported grants from Cue Biopharma during the conduct of the study. M.L. Dustin reported grants from Cue Biopharma during the conduct of the study. No other disclosures were reported."

"We would like to thank the patients and their families. We are also grateful to Edwin de Zoeten, MD, PhD, and Paul Jedlicka, MD, PhD, for their intellectual input and helpful comments. Simulations performed by J.C. Gumbart, A. Acharya, and K. Lundquist were run on the Extreme Science and Engineering Discovery Environment (XSEDE, TG-MCB130173), which was supported by the National Science Foundation (ACI-1548562). We thank the HIMSR (RRID: SCR_021985) within the University of Colorado Human Immunology and Immunotherapy Initiative and the University of Colorado Cancer Center (P30CA046934) for their expert assistance with multispectral imaging on the Vectra 3.0 platform. The authors appreciate the contribution to this research made by E. Erin Smith, histotechnologist (HTL) American Society for Clinical Pathology (ASCP), continuing medical education (CM), qualification in immunohistochemistry (QIHC); Allison Quador, HTL (ASCP) CM; and Jessica Arnold HTL (ASCP) CM of the University of Colorado Cancer Center Pathology Shared Resource (RRID: SCR_201994). This resource is supported in part by the Cancer Center Support Grant (P30CA046934). We thank The University of Colorado ImmunoMicro Flow Cytometry Shared Resource Laboratory, especially Tinalyn Kupfer, PhD, for her assistance with multispectral flow cytometry. We thank the University of Colorado Anschutz Medical Campus ImmunoMicro Flow Cytometry Shared Resource (RRID: SCR_021321). Figure graphics were generated using BioRender. V.G. Lui is supported by the Immunology Training Program T32 AI07405 and the National Science Foundation Graduate Research Fellowship NSF GRFP DGE-1938058. E.W.Y. Hsieh is supported by the Jeffrey Modell Foundation Translational Research Award and National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases K23AR070897. J. Capera is a Cancer Research Institute Irvington Fellow supported by the CRI4503. M.L. Dustin is supported by the Kennedy Trust for Rheumatology Research Cell Dynamics Platform with additional support from the Wellcome Trust (100262Z/12/Z and 224343/Z/21/Z)."