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

Junghans, Victoria LU ; Chouliara, Manto LU ; Santos, Ana Mafalda ; Hatherley, Deborah ; Petersen, Jan ; Dam, Tommy LU ; Svensson, Lena M. LU ; Rossjohn, Jamie ; Davis, Simon J. and Jönsson, Peter LU orcid (2020) In Journal of Cell Science 133(15).
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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Affinity, CD2, Lamellipodia, Major histocompatibility complex, Protein binding, T-cell receptor
in
Journal of Cell Science
volume
133
issue
15
article number
jcs245985
publisher
The Company of Biologists Ltd
external identifiers
  • pmid:32591485
  • scopus:85089128116
ISSN
0021-9533
DOI
10.1242/jcs.245985
language
English
LU publication?
yes
id
2d461d59-07fa-490d-be35-1a4e5991354c
date added to LUP
2020-08-18 08:27:49
date last changed
2024-12-27 17:01:40
@article{2d461d59-07fa-490d-be35-1a4e5991354c,
  abstract     = {{<p>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.</p>}},
  author       = {{Junghans, Victoria and Chouliara, Manto and Santos, Ana Mafalda and Hatherley, Deborah and Petersen, Jan and Dam, Tommy and Svensson, Lena M. and Rossjohn, Jamie and Davis, Simon J. and Jönsson, Peter}},
  issn         = {{0021-9533}},
  keywords     = {{Affinity; CD2; Lamellipodia; Major histocompatibility complex; Protein binding; T-cell receptor}},
  language     = {{eng}},
  number       = {{15}},
  publisher    = {{The Company of Biologists Ltd}},
  series       = {{Journal of Cell Science}},
  title        = {{Effects of a local auxiliary protein on the two-dimensional affinity of a TCR-peptide MHC interaction}},
  url          = {{http://dx.doi.org/10.1242/jcs.245985}},
  doi          = {{10.1242/jcs.245985}},
  volume       = {{133}},
  year         = {{2020}},
}