Docket #: S20-371
Direct Detection of T cell Mediated Immune Responses Using Peptide MHCs (pMHCs) Displayed on Multimeric Protein Scaffolds
The recognition of peptide-MHC (pMHC) complexes by T cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells. pMHC can thus be leveraged as a detection tool for T cells. The molecule naturally exists in a monomeric form, which impedes easy detection of T cells due to their weak equilibrium dissociation with the lymphocyte. To overcome this limitation, inventors at Stanford have developed a flexible pMHC display system on a self-assembling protein scaffold. Termed a spheromer, the platform has high compatibility with currently available pMHC molecules and streptavidin reagents that are routinely used for T cell analysis. Due to its increased specificity and sensitivity, the pMHC-spheromer platform overcomes the current limitations of existing T cell detection platforms. The platform is a valuable tool that can be used for the detection, isolation, and activation of antigen-specific T cells, enabling the successful tracking and modulation of the adaptive immune response.
Applications
- Detection and quantitation of disease-relevant T-cells
- Disease tracking, such as immunity in vaccinated individuals
- Induction of antigen-specific immunological tolerance to treat autoimmune conditions
Advantages
- Greater detection efficiency than any commonly used pMHC multimer reagents
- Customizable system enabling addition of co-stimulator molecules
- Modulation of anti-tumor/anti-viral immunity by inducing antigen-specific responses
Publications
- Mallajosyula et al. (2021). CD8+ T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients. Science Immunology, Vol 6, Issue 61.
Additional Related Publications
- Vamsee Mallajosyula, Mark.M. Davis et al. (2023). Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection. Immunity, Volume 56, Issue 4, Pages 864-878.e4, ISSN 1074-7613.
- Vamsee Mallajosyula, Mark M Davis et al. (2024). HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease, Brain, awae048.
Related Links
Patents
- Published Application: WO2022133347
- Published Application: 20240076356
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