CD5 inhibits signaling at the immunological synapse without impairing its formation.
Physiologically, Ag detection by T cells occurs at the immunological synapse (IS) formed at the interface with an APC. CD5 is considered as an inhibitory molecule for Ag receptor-mediated signals in T cells. However, the influence of CD5 at the IS on synapse formation and functioning has not yet been reported. We demonstrate here that CD5 is recruited and tightly colocalized with CD3 in different human and murine IS. Following transfection in a CD5-negative T cell line of CD5 fused to the green fluorescent protein, we show that CD5 recruitment includes a fast Ag-independent and a slower Ag-dependent component. In video-imaging recordings of doubly transfected cells, the movements of CD3 and CD5 show similar kinetics, and the amount of CD3 recruited to the synapse is unaffected by CD5 expression. Moreover, APC-T cell adhesion is unchanged in CD5-expressing cells. Despite this, the extent of tyrosine phosphorylation at the synapse and the amplitude of calcium responses induced by Ag recognition are both decreased by CD5. These inhibitions increase with CD5 membrane levels. They also requires the pseudo-immunoreceptor tyrosine-based activation motif expressed in the cytoplasmic domain of the molecule. Thus, CD5 is rapidly recruited at the IS and lowers the T cell response elicited by Ag presentation by targeting downstream signaling events without affecting IS formation.
Brossard
Cédric
C
Département de Biologie Cellulaire, Institut National de la Santé et de la Recherche Médicale, Unité 567, Center National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Université René Descartes, Institut Cochin, Paris, France.
Semichon
Monique
M
Trautmann
Alain
A
Bismuth
Georges
G
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D017252:CD3 Complex / Q000378:metabolism; D018956:CD5 Antigens / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D019169:Jurkat Cells; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D018956:CD5 Antigens; D046911:Macromolecular Substances