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

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

^*Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; and ^‡Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115

Contributed by Susumu Tonegawa

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-2D^b 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.

thymus/positive selection

Footnotes

↵ † To whom reprint requests should be addressed at: Center for Cancer Research, Room E17-353, Massachusetts Institute of Technology, 40 Ames Street, Cambridge, MA 02139. e-mail: clevelt{at}wccf.mit.edu.
ABBREVIATIONS:

SP,

single positive;

DP,

double positive;

TCR,

T cell receptor;

FACS,

fluorescence-activated cell sorter;

MHC,

major histocompatibility complex