Control of T-cell Development by the TCR for Antigen

Abstract

Experiments concerned with the selection of the T-cell repertoire have a relatively long history and were conducted even before we knew about the T-cell receptor (TCR) and antigen-presenting major histocompatibility complex (MHC) molecules. Early experiments consistent with clonal deletion (von Boehmer and Sprent 1976; Good et al. 1983) as well as with positive selection (Bevan 1977; von Boehmer et al. 1978; Kappler and Marrack 1978; Zinkernagel et al. 1978) were the subject of much debate because of the indirect nature of these experiments. At the time, it was impossible to reach firm conclusions about mechanisms and extent of selection. Evidence for deletion, for instance, rested on negative experiments failing to reveal suppression in tolerant animals. In addition, it was not clear whether or not deletion could occur at any stage of T-cell development or, as suggested by Lederberg (1959), had to occur early in development. Experiments concerned with positive selection...