Microfluidic assay analyzes initiation of adaptive immune response

T-cell receptors (TCR) initiate the cell-mediated immune response by recognizing and binding to peptide-major histocompatibility complex (pMHC) molecules displaying foreign antigens. However, determining the binding strength of this interaction has been difficult to achieve for high throughput.

A microfluidic “trap array” platform allows for detection of specific TCR-pMHC interactions by measuring T-cell speed changes as a predictor of interaction strength. Researchers used optical microscopy to track speeds of T-cells in a microfluidic device as the cells interacted with pMHC-coated beads contained in hydrodynamic traps. The specificity and affinity of TCR-pMHC interactions from the measurements using these assays is reported in Biomicrofluidics.

Speed-based affinity measurements detected specific TCR-pMHC interactions using the trap array platform. As T-cells approached pMHC beads, they slowed in conjunction with their antigen interaction level. The range of detectable interaction forces could be adjusted by altering T-cell flow rate through the assay, with decreased flow rate for low-affinity interactions and increased flow rate for high-affinity.

Microfluidic trap array systems can also be expanded to analyze any type of cell-receptor interactions, in addition to T-cell and antigen binding. The use of fluorescence imaging along with this array could provide increasingly detailed information about T-cells and their interactions. “By preparing beads with different combinations of TCR and co-receptors, this approach could be used to determine the necessary/sufficient conditions for T-cell activation in different model systems,” said Max Stockslager, an author of the paper.

Source: “Microfluidic platform for characterizing TCR-pMHC interactions,” by Max A. Stockslager, Josephine Shaw Bagnall, Vivian C. Hecht, Kevin Hu, Edgar Aranda-Michel, Kristofor Payer, Robert J. Kimmerling, and Scott R. Manalis, Biomicrofluidics (2017). The article can be accessed at https://doi.org/10.1063/1.5002116 .