title: Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest.
abstract: T lymphocytes are highly motile cells that decelerate upon antigen recognition. These cells can either completely stop or maintain a low level of motility, forming contacts referred to as synapses or kinapses, respectively. Whether similar or distinct molecular mechanisms regulate T-cell deceleration during synapses or kinapses is unclear. Here, we used microfabricated channels and intravital imaging to observe and manipulate T-cell kinapses and synapses. We report that high-affinity antigen induced a pronounced deceleration selectively dependent on Ca(2+) signals and actin-related protein 2/3 complex (Arp2/3) activity. In contrast, low-affinity antigens induced a switch of migration mode that promotes T-cell exploratory behavior, characterized by partial deceleration and frequent direction changes. This switch depended on T-cell receptor binding but was largely independent of downstream signaling. We propose that distinct mechanisms of T-cell deceleration can be triggered during antigenic recognition to favor local exploration and signal integration upon suboptimal stimulus and complete arrest on the best antigen-presenting cells.
authors.affiliation: Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France; INSERM U668, 75015 Paris, France; Cellule Pasteur, Sorbonne Paris Cité, University Paris Diderot, 75015 Paris, France;
authors.forename: Hélène D
authors.initials: HD
authors.lastname: Moreau
authors.affiliation: Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France; INSERM U668, 75015 Paris, France;
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lemaître
authors.affiliation: Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France; INSERM U668, 75015 Paris, France;
authors.forename: Kym R
authors.initials: KR
authors.lastname: Garrod
authors.affiliation: Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France; INSERM U668, 75015 Paris, France;
authors.forename: Zacarias
authors.initials: Z
authors.lastname: Garcia
authors.affiliation: INSERM U932, Institut Curie, 75005 Paris, France.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Lennon-Duménil
authors.affiliation: Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France; INSERM U668, 75015 Paris, France; philippe.bousso@pasteur.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D060833:Cellular Microenvironment / Q000276:immunology*; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000276:immunology*; D054992:Immunological Synapses / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium
keywords: T cell; kinapse; migration; synapse