TCR Inhibitory Peptides for Blocking pMHC-Driven T Cell Activation
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Solution Overview
Problem
Current methods rely on T cell receptors (TCRs) interacting with peptide-major histocompatibility (pMHC) complexes, which can lead to unwanted immune responses, and there is a need for inhibiting these interactions to control T cell activation.
Innovation Solution
Administering inhibitory peptides that bind directly to TCRs without the aid of MHC, blocking the interaction with pMHC complexes, using methods to identify and characterize these peptides through peptide libraries and pH-based binding assays.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TCRs interact with pMHC complexes to recognize antigens, then immune response activation is achieved, but autoimmune responses occur due to inability to distinguish self from non-self
Solution Approach 1:
The patent introduces MHC molecules as intermediaries between TCRs and antigens. The TCR does not directly bind to free antigens but only to antigens presented by MHC molecules, allowing the immune system to distinguish between self and non-self through MHC restriction. This mediator mechanism prevents autoimmune responses while maintaining effective immune activation.
Solution Approach 2:
The patent extracts the antigen recognition function from direct TCR-antigen interaction and separates it into two distinct components: MHC molecules that present the antigen and TCRs that recognize the MHC-presented antigen. This separation allows for selective recognition of foreign antigens while ignoring self-antigens, thereby preventing autoimmune responses.
2Adaptability or versatility
If TCRs can recognize any antigen directly, then broad antigen detection is achieved, but specificity control is lost leading to unwanted immune responses
Solution Approach 1:
MHC molecules serve as mandatory intermediaries that control which antigens can be recognized by TCRs. The MHC-TCR interaction adds a layer of specificity control, ensuring that T cells only respond to antigens that are properly presented by MHC molecules, thus maintaining immune response specificity while preserving broad antigen detection capability through diverse MHC alleles.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Inhibitory peptides effectively block TCR-pMHC interactions, providing control over T cell activation and reducing unwanted immune responses.
Implementation Method 1
the inhibitory peptide binds to the TCR through ionic interactions, electrostatic interactions, hydrophobic interactions, Pi-stacking interactions, and H-bonding interactions
Implementation Method 2
the inhibitory peptide binds to the TCR through ionic interactions, electrostatic interactions, hydrophobic interactions, Pi-stacking interactions, and H-bonding interactions
Implementation Method 3
the inhibitory peptide binds to the TCR through ionic interactions, electrostatic interactions, hydrophobic interactions, Pi-stacking interactions, and H-bonding interactions
Implementation Method 4
the inhibitory peptide binds to the TCR through ionic interactions, electrostatic interactions, hydrophobic interactions, Pi-stacking interactions, and H-bonding interactions
Data Source
AI summary
Disclosed herein are methods of inhibiting an interaction of a T cell receptor with a peptide-major histocompatibility complex comprising administering inhibitory peptides that bind to the T cell receptor without the aid of a major histocompatibility complex to inhibit the interaction, and methods of identifying the inhibitory peptides.