Year: 2023
Type: conference-abstract
Abstract: Lupus nephritis (LN) is the most common severe organ manifestation of Systemic lupus erythematosus (SLE). Autoreactive CD4+ T cells play a key role in SLE, but the mechanism of loss of self-tolerance and antigen specificity of CD4+ T cells is unclear. CD4+ αβ T cells use their T cell receptor (TCR) to recognize 12–20 residue-long epitopes presented on class II MHC molecules. Identifying CD4+ T cell epitopes has been challenging due to lack of efficient and easy-to-implement methods for epitope discovery. We developed a robust T cell antigen discovery technology that uses chimeric receptors called SABR-II (Signaling and Antigen-presenting Bifunctional Receptors) to express large peptide antigen libraries in the context of MHC molecules. Using SABR-IIs, we sought to identify the autoantigens recognized by kidney-infiltrating CD4+ T cells in a mouse mode of LN – MRL/lpr mice. We used a high-throughput single cell TCR cloning to clone and express 93 TCRs from CD4+ T cells sorted from kidneys of 26-week-old MRL/lpr mice. For antigen discovery, we constructed SABR-IIs with I-Ek and I-Ak (class II MHC allele of MRL/lpr mice) and confirmed their functionality. We built libraries of ~25,000 epitopes derived from nuclear proteins and validated them using a known antigen-specific TCR. We have identified novel putative autoantigens, which will be validated in vitro. This study will lead to identification of novel self-antigens, providing the groundwork for understanding the biology of LN and for development of preventative and therapeutic approaches in SLE.
Source: The Journal of Immunology
Authors: Sanya Arshad, David Gao, Lyubov Kublo, Alex Rowe, Wenzhong Wei, Yi Yang, Mark Jay Shlomchik, Jeremy Tilstra, Alok Joglekar
Institution: University of Pittsburgh
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4385685380