title: Inhibition of intrathymic T cell development by expression of a transgenic antagonist peptide.
abstract: The mature T cell receptor (TCR) repertoire is shaped by positive- and negative-selection events taking place during T cell development. These events are regulated by interactions between the TCR and major histocompatibility complex molecules presenting self-peptides. It has been shown that many antagonist peptides are efficient at mediating positive selection. In this study we analyzed the effects of a transgene encoding an antagonist peptide (influenza NP34) that is presented by H-2Db in a Tap-1-independent fashion in mice expressing the influenza NP68-specific TCR F5. We find that the transgenic peptide does not mediate positive or negative selection in F5(+)Tap-1(-/-) mice, but inhibits maturation of CD8(+) single positive thymocytes in F5(+)Tap-1(+) mice without inducing signs of negative selection. We conclude that antagonism of antigen recognition occurs not only at the level of mature T cells but also in T cell development.
authors.affiliation: Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. clevelt@wccf.mit.edu
authors.forename: C N
authors.initials: CN
authors.lastname: Levelt
authors.forename: E
authors.initials: E
authors.lastname: Mizoguchi
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Zacks
authors.forename: A K
authors.initials: AK
authors.lastname: Bhan
authors.forename: S
authors.initials: S
authors.lastname: Tonegawa
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D020287:In Situ Nick-End Labeling; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse