Distinctive selection mechanisms govern the T cell receptor repertoire of peripheral CD4-CD8- α/β T cells

Abstract

The T cell receptor (TCR) repertoire of CD4+ and CD8+ α/β cells is heavily influenced by positive and negative selection events that occur during T cell development in the thymus. The coreceptors CD4 and CD8 appear to be essential for this selection to occur. To gain insight into whether T cells that express TCR α/β but lack either coreceptor (CD4- CD8- TCR α/β or α/β double-negative [DN] cells) are also subject to positive and negative selection, and whether selection can occur in the absence of coreceptors, we have performed an extensive immunogenetic analysis of the TCR Vβ repertoire of α/β DN cells in lymph nodes of normal mice. Our results show that α/β DN cells appear to be unaffected by clonal deletion of Vβ5 and Vβ11 in I-E-expressing mice, and do not undergo deletion of Vβ6- and Vβ8.1-expressing T cells in Mls-1a-positive mice. They are also unaffected by positive selection of Vβ17a+ T cells in the context of I-Aq. The results suggest that most selection events require the participation of CD4 and CDS, while α/β DN cells are unselected. This argues that most α/β DN cells probably have never expressed CD4 or CD8. However, a unique form of repertoire selection occurs: enrichment of Vβ17a+ α/β DN cells in I-E+ mice. This could be an instance of coreceptor-independent selection.