Evaluation of TCR-pMHC affinity and its implications for T cell responsiveness

In the adaptive immune response, interactions between the T cell receptor (TCR) and the major histocompatibility complex (MHC) are crucial for immune system development, maturation, surveillance, and protection against pathogens and cancer.

When the TCR binds to a pMHC complex, in conjunction with co-stimulatory signals and environmental cytokines, it triggers a cascade of intracellular signalling events that ultimately lead to T cell activation. TCR affinity for pMHC is relatively weak in vivo, with a KD in the micromolar range. By modifying this interaction, it is possible to enhance or suppress the immune response, providing a powerful tool for therapeutic intervention.

Understanding the TCR-pMHC interaction is essential for developing new therapies for autoimmune disorders, infectious diseases, and cancers, as well as for the development of screening and diagnostic tools.

Read the full application note to learn more about measuring TCR-pMHC affinity.

Highlights

In this application note, our partner Quality Assistance studied the interaction between a modified affinity-enhanced TCR (expected to have nanomolar affinity) targeting the NY-ESO I antigen (Immudex cat. no. CSS009M) and pMHC (MHC Monomer, HLA-A*0201/SLLMWITQC, cat. no. WB02696M). Both TCR and pMHC monomers were manufactured and supplied by Immudex through Custom Solutions and Services.
TCR-pMHC affinity and kinetics were analyzed using both surface plasmon resonance (SPR, Biacore) and biolayer interferometry (BLI, Octet) techniques, and the performance of the two techniques was compared.

Based on the characteristics of the technology and the results obtained, BLI is the method of choice to measure the affinity of the TCR-pMHC interaction and provide reliable results for deciding on optimal TCR engineering, using a biotinylated soluble TCR monomer and a His-tagged unbiotinylated pMHC.

Download the Application Note

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