Antigen-specific modulation of autoimmunity by TCR-like antibody targeting autoreactive T-cell epitope.

Author : Yoram Reiter

Abstract :The development and application of human TCR-like (TCRL) antibodies recognizing disease-specific MHC-peptide complexes may prove as an important tool for basic research and therapeutic applications. Multiple sclerosis is characterized by aberrant CD4 T-cell response to self-antigens presented by MHC class II molecules. This led us to select a panel of TCRL Abs targeting the immunodominant autoantigenic epitope MOG35-55 derived from myelin oligodendrocyte glycoprotein (MOG) presented on HLA DR2, which is associated with multiple sclerosis (MS). We demonstrate that these TCRL Abs bind with high specificity to human HLA DR2/MOG35-55-derived MHC class II molecules and can detect APCs that naturally present the MS-associated autoantigen in the humanized EAE transgenic mouse model. The TCRL Abs can block ex vivo and in vivo CD4 T-cell proliferation in response to MOG35 55 stimulation in an antigen specific manner. Most significantly, administration of TCRL Abs to MOG35-55 induced EAE model in HLA DR2 transgenic mice both prevents and regresses established EAE. TCRL function was associated with a reduction in autoreactive pathogenic T-cell infiltration into the CNS, along with modulation of activated CD11b+ macrophages/microglial APCs. Collectively, these findings demonstrate the combined action of TCRL Abs in blocking TCR-MHC interactions and modulating APC presentation and activation, leading to a profound antigen specific inhibitory effect on the neuroinflammatory process, resulting in regression of EAE. Our study constitutes an in vivo proof of concept for the utility of TCR-like antibodies as antigen-specific immunomodulators for CD4-mediated autoimmune diseases such as MS, validating the importance of the TCR-MHC axis as a therapeutic target for various autoimmune and inflammatory diseases

Keywords :TCR-like antibodies, MHC-peptide complexes, Multiple sclerosis, CD4 T-cells, Autoimmune therapy

Conference Name :International Conference on Auto Immune Diseases and Healthcare (ICAIDH-25)

Conference Place Phuket,Thailand

Conference Date 8th Dec 2025