Impact of TCR-peptide/MHC class II affinity on the pathogenicity and regulation of prostate-specific CD4+ T cells

• DOI: 10.4049/jimmunol.208.supp.169.15
• Publication Date: 2023-01-02T16:11:21Z
• Authors: Donald M Rodriguez; Ryan Duncombe; Victoria Lee; Sharon Zeng; David E J Klawon; Erin J Adams; Peter Aidan Savage
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract In both humans and mice, self-reactive CD4+ T cells are implicated in a range of autoinflammatory processes. To promote disease, such must evade clonal deletion the thymus, as well intrinsic extrinsic regulation mechanisms periphery, including anergy regulatory cell-mediated suppression. However, impact cell receptor (TCR) - peptide/MHC class II (pMHCII) binding properties on autoimmune potential self-specific their susceptibility to immune remains incompletely defined. Much previous work this topic has relied study reactive foreign model antigens. responses towards antigens may not recapitulate those targeting bona fide self-antigens. Through vivo analysis clones natural I-Ab-restricted self-peptide derived from prostate-specific protein Tcaf3 (termed “C4” peptide), we aim define role TCR-pMHCII affinity pathogenicity clones. Our findings thus far tumor-free prostate-tumor-bearing mice reveal notable differences developmental trajectories peripheral functions with varying TCR for C4/I-Ab. Ongoing will continue leverage our novel physiologically relevant TCR-ligand system better understand fundamental by which tolerance is established enforced. This was funded following sources (to P.A.S.): R01-CA160371, R01-AI110507, U01-AI154560, Cancer Research Institute Investigator Award, University Chicago Comprehensive Center. D.R. supported an NIH/NCI F30 predoctoral fellowship (F30-CA247264). V.L. (F30-CA217109). were Medical Scientist Training Program (T32-GM007281).