Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity

Area of Science:

• Immunology
• Cellular Biology
• Biophysics

Background:

• T cell receptor (TCR) signaling is initiated by peptide-MHC (pMHC) binding to T cells on antigen-presenting cells (APCs).
• The precise mechanism of TCR triggering remains unclear, particularly why soluble pMHCs are ineffective while surface-bound pMHCs are potent activators.

Purpose of the Study:

• To identify critical APC-associated factors responsible for the high potency of agonist pMHCs in TCR triggering.
• To elucidate the biophysical requirements for efficient TCR signal initiation.

Main Methods:

• Utilized artificial APCs, including fluid lipid bilayers and fixed plastic surfaces, presenting defined pMHC ligands.
• Investigated the role of surface properties and T cell cytoskeleton dynamics in TCR triggering using CD4+ T cells.

Main Results:

• CD4+ T cells were triggered by low numbers of monomeric agonist pMHCs on fluid bilayers or fixed surfaces, independent of other APC molecules.
• TCR triggering efficiency was critically dependent on surface adhesiveness and an intact T cell actin cytoskeleton.
• Endogenous pMHCs did not enhance TCR triggering on artificial surfaces or real APCs.

Conclusions:

• Surface-bound pMHCs trigger TCRs efficiently due to surface adhesiveness and T cell actin cytoskeleton involvement.
• Proposes the receptor deformation model to explain the sensitivity and specificity of TCR triggering.