scholarly journals Cooperative Stabilization of Close-Contact Zones Leads to Sensitivity and Selectivity in T-Cell Recognition

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1023
Author(s):  
Bartosz Różycki ◽  
Thomas Weikl
Keyword(s):  
Cell Adhesion ◽  
T Cell ◽  
Close Contact ◽  
Three Dimensional ◽  
Cell Recognition ◽  
Contact Zones ◽  
T Cell Recognition ◽  
Foreign Peptide ◽  
Sensitivity And Selectivity ◽  
T Cell Adhesion

T cells are sensitive to 1 to 10 foreign-peptide-MHC complexes among a vast majority of self-peptide-MHC complexes, and discriminate selectively between peptide-MHC complexes that differ not much in their binding affinity to T-cell receptors (TCRs). Quantitative models that aim to explain this sensitivity and selectivity largely focus on single TCR/peptide-MHC complexes, but T cell adhesion involves a multitude of different complexes. In this article, we demonstrate in a three-dimensional computational model of T-cell adhesion that the cooperative stabilization of close-contact zones is sensitive to one to three foreign-peptide-MHC complexes and occurs at a rather sharp threshold affinity of these complexes, which implies selectivity. In these close-contact zones with lateral extensions of hundred to several hundred nanometers, few TCR/foreign-peptide-MHC complexes and many TCR/self-peptide-MHC complexes are segregated from LFA-1/ICAM-1 complexes that form at larger membrane separations. Previous high-resolution microscopy experiments indicate that the sensitivity and selectivity in the formation of closed-contact zones reported here are relevant for T-cell recognition, because the stabilization of close-contact zones by foreign, agonist peptide-MHC complexes precedes T-cell signaling and activation in the experiments.

scholarly journals Cooperative Stabilization of Close-Contact Zones Leads to Sensitivity and Selectivity in T-Cell Recognition

2021 ◽  
Author(s):  
Bartosz Różycki ◽  
Thomas R. Weikl
Keyword(s):  
Cell Adhesion ◽  
T Cell ◽  
Close Contact ◽  
Three Dimensional ◽  
Cell Recognition ◽  
Contact Zones ◽  
T Cell Recognition ◽  
Foreign Peptide ◽  
Sensitivity And Selectivity ◽  
T Cell Adhesion

AbstractT cells are sensitive to 1 to 10 foreign-peptide-MHC complexes among a vast majority of self-peptide-MHC complexes, and discriminate selectively between peptide-MHC complexes that differ not much in their binding affinity to T-cell receptors (TCRs). Quantitative models that aim to explain this sensitivity and selectivity largely focus on single TCR/peptide-MHC complexes, but T cell adhesion involves a multitude of different complexes. In this article, we demonstrate in a three-dimensional computational model of T-cell adhesion that the cooperative stabilization of close-contact zones is sensitive to 1 to 3 foreign-peptide-MHC complexes and occurs at a rather sharp threshold affinity of these complexes, which implies selectivity. In these close-contact zones with lateral extensions of hundred to several hundred nanometers, few TCR/foreign-peptide-MHC complexes and many TCR/self-peptide-MHC complexes are segregated from LFA-1/ICAM-1 complexes that form at larger membrane separations. Previous high-resolution microscopy experiments indicate that the sensitivity and selectivity in the formation of closed-contact zones reported here is relevant for T-cell recognition, because the stabilization of close-contact zones by foreign, agonist peptide-MHC complexes precedes T-cell signaling and activation in the experiments.

scholarly journals Changes at peptide residues buried in the major histocompatibility complex (MHC) class I binding cleft influence T cell recognition: a possible role for indirect conformational alterations in the MHC class I or bound peptide in determining T cell recognition.

1993 ◽  
Vol 177 (3) ◽  
pp. 869-873 ◽  
Author(s):  
W Chen ◽  
J McCluskey ◽  
S Rodda ◽  
F R Carbone
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Conformational Changes ◽  
Direct Interaction ◽  
Cell Receptor ◽  
Class I ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
Foreign Peptide ◽  
Binding Cleft

Recent crystallographic studies on two peptide complexes with the mouse Kb molecule have shown that peptide binding appears to alter the conformation of the class I alpha-helical regions that flank the antigen binding cleft. Given that this study also showed that much of the foreign peptide is buried within the class I binding cleft with only a small portion accessible for direct interaction with the components of the T cell receptor, this finding suggests that at least some component of T cell specificity may arise as a consequence of peptide-induced conformational changes in the class I structure. To assess this possibility, we have made systematic substitutions at residues within the Kb-restricted determinant from ovalbumin (OVA257-264) that are thought to be buried on binding to the class I molecule. We have found that changes in this determinant at the completely buried second residue (P2) can influence T cell recognition without affecting binding to Kb, suggesting that the substitutions may indirectly determine T cell recognition by altering the conformation of the class I molecule or the bound peptide.

scholarly journals Three-Dimensional Model of Sub-Plasmalemmal Ca2+ Microdomains Evoked by the Interplay Between ORAI1 and InsP3 Receptors

2021 ◽  
Vol 12 ◽  
Author(s):  
Diana Gil ◽  
Andreas H. Guse ◽  
Geneviève Dupont
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Three Dimensional ◽  
Receptor Activation ◽  
Reaction Diffusion Model ◽  
Activated State ◽  
T Cell Adhesion

Ca2+ signaling plays an essential role in T cell activation, which is a key step to start an adaptive immune response. During the transition from a quiescent to a fully activated state, Ca2+ microdomains characterized by reduced spatial and temporal extents are observed in the junctions between the plasma membrane (PM) and the endoplasmic reticulum (ER). Such Ca2+ responses can also occur in response to T cell adhesion to other cells or extracellular matrix proteins in otherwise unstimulated T cells. These non-TCR/CD3-dependent Ca2+ microdomains rely on d-myo-inositol 1,4,5-trisphosphate (IP3) signaling and subsequent store operated Ca2+ entry (SOCE) via the ORAI/STIM system. The detailed molecular mechanism of adhesion-dependent Ca2+ microdomain formation remains to be fully elucidated. We used mathematical modeling to investigate the spatiotemporal characteristics of T cell Ca2+ microdomains and their molecular regulators. We developed a reaction-diffusion model using COMSOL Multiphysics to describe the evolution of cytosolic and ER Ca2+ concentrations in a three-dimensional ER-PM junction. Equations are based on a previously proposed realistic description of the junction, which is extended to take into account IP3 receptors (IP3R) that are located next to the junction. The first model only considered the ORAI channels and the SERCA pumps. Taking into account the existence of preformed clusters of ORAI1 and STIM2, ORAI1 slightly opens in conditions of a full ER. These simulated Ca2+ microdomains are too small as compared to those observed in unstimulated T cells. When considering the opening of the IP3Rs located near the junction, the local depletion of ER Ca2+ allows for larger Ca2+ fluxes through the ORAI1 channels and hence larger local Ca2+ concentrations. Computational results moreover show that Ca2+ diffusion in the ER has a major impact on the Ca2+ changes in the junction, by affecting the local Ca2+ gradients in the sub-PM ER. Besides pointing out the likely involvement of the spontaneous openings of IP3Rs in the activation of SOCE in conditions of T cell adhesion prior to full activation, the model provides a tool to investigate how Ca2+ microdomains extent and interact in response to T cell receptor activation.

scholarly journals T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

2002 ◽  
Vol 87 (9) ◽  
pp. 1034-1041 ◽  
Author(s):  
J J French ◽  
J Cresswell ◽  
W K Wong ◽  
K Seymour ◽  
R M Charnley ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Adhesion ◽  
T Cell ◽  
Cancer Cells ◽  
Pancreatic Cancer Cells ◽  
E Cadherin ◽  
T Cell Adhesion

scholarly journals Topoisomerase inhibitors modulate expression of melanocytic antigens and enhance T cell recognition of tumor cells

2010 ◽  
Vol 60 (1) ◽  
pp. 133-144 ◽  
Author(s):  
Timothy J. Haggerty ◽  
Ian S. Dunn ◽  
Lenora B. Rose ◽  
Estelle E. Newton ◽  
Sunil Martin ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Cell Recognition ◽  
Topoisomerase Inhibitors ◽  
T Cell Recognition

Structural and ICAM-1-Docking Properties of a Cyclic Peptide from the I-domain of LFA-1: An inhibitor of ICAM-1/LFA-1-mediated T-cell adhesion

2002 ◽  
Vol 19 (5) ◽  
pp. 789-799 ◽  
Author(s):  
Christine R. Xu ◽  
Helena Yusuf-Makagiansar ◽  
Yongbo Hu ◽  
Seetharama D.S. Jois ◽  
Teruna J. Siahaan
Keyword(s):  
Cell Adhesion ◽  
T Cell ◽  
Cyclic Peptide ◽  
T Cell Adhesion

scholarly journals Augmentation of RANTES-Induced Extracellular Signal-Regulated Kinase Mediated Signaling and T Cell Adhesion by Elastase-Treated Fibronectin

2001 ◽  
Vol 166 (12) ◽  
pp. 7121-7127 ◽  
Author(s):  
Alexander Brill ◽  
Rami Hershkoviz ◽  
Gayle G. Vaday ◽  
Yehuda Chowers ◽  
Ofer Lider
Keyword(s):  
Cell Adhesion ◽  
T Cell ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
T Cell Adhesion

scholarly journals Cell-mediated lympholysis to H-2-matched target cells modified with a series of nitrophenyl compounds.

1976 ◽  
Vol 144 (4) ◽  
pp. 1134-1140 ◽  
Author(s):  
T G Rehn ◽  
J K Inman ◽  
G M Shearer
Keyword(s):  
T Cell ◽  
Target Cells ◽  
Cell Recognition ◽  
Receptor Model ◽  
Spleen Cells ◽  
Effector Cells ◽  
T Cell Recognition ◽  
Cytotoxic Effector

The specificity of C57BL/10 cytotoxic effector cells generated by in vitro sensitization with autologous spleen cells modified with a series of related nitrophenyl compounds was investigated. The failure of trinitrophenyl (TNP)-sensitized effector cells to lyse TNP-beta-alanylglycylglycyl(AGG)-modified target cells is presented as evidence contradicting the intimacy or dual receptor model or T-cell recognition in its simplest form. Data are also shown indicating that sensitization with N-(3-nitro-4-hydroxy-5-iodophenylacetyl)-AGG-modified stimulating cells generates noncross-reacting clones of cytotoxic effector cells.

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