Effects of a local auxiliary protein on the two-dimensional affinity of a TCR-peptide MHC interaction

Research output: Contribution to journalArticle

Abstract

The affinity of T-cell receptors (TCRs) for major histocompatibility complex molecules (MHCs) presenting cognate antigens likely determines whether T cells initiate immune responses, or not. There exist few measurements of two-dimensional (2D) TCR-MHC interactions, and the effect of auxiliary proteins on binding is unexplored. Here, Jurkat T-cells expressing the MHC molecule HLA-DQ8-glia-α1 and the ligand of an adhesion protein (rat CD2) were allowed to bind supported lipid bilayers (SLBs) presenting fluorescently labelled L3-12 TCR and rat CD2, allowing measurements of binding unconfounded by cell signaling effects or co-receptor binding. The 2D Kd for L3-12 TCR binding to HLA-DQ8-glia-α1, of 14±5 molecules/μm2 (mean±s.d.), was only marginally influenced by including CD2 up to ∼200 bound molecules/μm2 but higher CD2 densities reduced the affinity up to 1.9-fold. Cell-SLB contact size increased steadily with ligand density without affecting binding for contacts at up to ∼20% of total cell area, but beyond this lamellipodia appeared, giving an apparent increase in bound receptors of up to 50%. Our findings show how parameters other than the specific protein-protein interaction can influence binding behavior at cell-cell contacts.

Details

Authors
Organisations
External organisations
  • University of Oxford
  • Monash University
  • Örebro University
  • John Radcliffe Hospital
  • Cardiff University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology

Keywords

  • Affinity, CD2, Lamellipodia, Major histocompatibility complex, Protein binding, T-cell receptor
Original languageEnglish
Article number jcs245985
JournalJournal of Cell Science
Volume133
Issue number15
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes