MHC Class II Molecules with Enhanced Co-receptor Affinity

IP Status: US Patent Issued; Patent No. 12,187,781

Applications

• New generation of peptide:MHCII tetramer products
• T cell detection in flow cytometry
• Reagents
• Research tool

Key Benefits & Differentiators

• Improved capture of antigen specific CD4 T cells: Enhanced binding to the CD4 co-receptor developed through a directed evolution process
• Benefit: Features that provide the benefit

Better binding affinity for co-receptor CD4

Current methods for detecting and understanding specific types of T cells are imperfect. A CD4 T cell uses its unique T-cell receptor (TCR) molecules to bind to a foreign peptide embedded in an MHCII molecule on host cells. At the same time, the T cell’s CD4 molecules bind to the stalk of the MHCII molecules and cooperate with the TCR to activate the T cell. Peptide:MHCII tetramer-based flow cytometry is a preferred method for the study of CD4 T cells specific for MHCII-bound peptides from microbes, cancers, and autoantigens. Unfortunately, peptide:MHCII tetramers do not bind to CD4 molecules and therefore fail to detect CD4 T cells with low affinity TCRs.

Higher affinity than wild-type MHCII molecules

Researchers at the University of Minnesota have developed enhanced-affinity MHCII molecules as an improved research tools for the study of CD4 T cells during cancer, infection, and autoimmune disease. A novel process uses directed evolution to create modified MHCII molecules with better binding affinity than their wild-type counterparts for the co-receptor CD4 found on T cell surfaces. This new technology creates a new generation of modified MHCII molecules evolved to bind CD4 with stronger affinity than wild-type MHCII molecules. Tetramers formed with peptide-bound CD4 affinity-enhanced MHCII tetramers detect T cells that are missed by peptide-bound wild-type MHCII tetramers. This technology allows researchers to detect more relevant T cells than currently possible.

Phase of Development

TRL: Platform technology: 3-4, Select individual tetramers: 5

Desired Partnerships

This technology is now available for:

• License
• Sponsored research
• Co-development

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Researchers

• Marc Jenkins, PhD Professor, Department of Microbiology & Immunology
• Thamotharampillai Dileepan, PhD Assistant Professor, Department of Microbiology and Immunology