title: Modeling TCR signaling complex formation in positive selection.
abstract: T cell receptor signaling in the thymus can result in positive selection, and hence progressive maturation to the CD4(+)8(-) or CD4(-)8(+) stage, or induction of apoptosis by negative selection. Although it is poorly understood how TCR ligation at the CD4(+)8(+) stage can lead to such different cell fates, it is thought that the strength of signal may play a role in determining the outcome of TCR signaling. In this study, we have characterized the formation of an active signaling complex in thymocytes undergoing positive selection as a result of interaction with thymic epithelial cells. Although this signaling complex involves redistribution of cell surface and intracellular molecules, reminiscent of that observed in T cell activation, accumulation of GM1-containing lipid rafts was not observed. However, enforced expression of the costimulatory molecule CD80 on thymic epithelium induced GM1 polarization in thymocytes, and was accompanied by reduced positive selection and increased apoptosis. We suggest that the presence or absence of CD80 costimulation influences the outcome of TCR signaling in CD4(+)8(+) thymocytes through differential lipid raft recruitment, thus determining overall signal strength and influencing developmental cell fate.
authors.affiliation: Department of Anatomy, Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom. K.J.Hare@bham.ac.uk
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Hare
authors.forename: Judit
authors.initials: J
authors.lastname: Pongracz
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jenkinson
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
mesh_terms: D000818:Animals; D015703:Antigens, CD; D017252:CD3 Complex / Q000378:metabolism; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D005677:G(M1) Ganglioside / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051917:Leukosialin; D008285:Major Histocompatibility Complex / Q000502:physiology; D021962:Membrane Microdomains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018448:Models, Immunological; D009924:Organ Culture Techniques; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012795:Sialoglycoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D051917:Leukosialin; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D005677:G(M1) Ganglioside; D017493:Leukocyte Common Antigens