Inhibition of intrathymic T cell development by expression of a transgenic antagonist peptide. NLM AIDSLINE Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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Inhibition of intrathymic T cell development by expression of a transgenic antagonist peptide.

Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14349-54. Unique Identifier : AIDSLINE MED/99045687
Levelt CN; Mizoguchi E; Huang X; Zacks R; Bhan AK; Tonegawa S; Center for Cancer Research, Massachusetts Institute of; Technology, Cambridge, MA 02139, USA. clevelt@wccf.mit.edu

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.
Keywords: JOURNAL ARTICLE Animal Apoptosis ABC Transporters/GENETICS/PHYSIOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY DNA Primers H-2 Antigens/GENETICS/IMMUNOLOGY Histocompatibility Antigens Class I/IMMUNOLOGY In Situ Nick-End Labeling Lymphocyte Transformation Major Histocompatibility Complex Mice Mice, Knockout Mice, Transgenic Peptides/*GENETICS/IMMUNOLOGY Polymerase Chain Reaction Receptors, Antigen, T-Cell/*GENETICS Support, U.S. Gov't, P.H.S. T-Lymphocytes/*IMMUNOLOGY Thymus Gland/*IMMUNOLOGY
990330
A9931031

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