DISTINCTIVE SELECTION MECHANISMS GOVERN THE T-CELL RECEPTOR REPERTOIRE OF PERIPHERAL CD4-CD8- ALPHA/BETA-T-CELLS

The T cell receptor (TCR) repertoire of CD4+ and CD8+ alpha/beta-T 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-alpha/beta but lack either coreceptor (CD4-CD8- TCR-alpha/beta or alpha/beta-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 V-beta repertoire of alpha/beta-DN cells in lymph nodes of normal mice. Our results show that alpha/beta-DN cells appear to be unaffected by clonal deletion of V-beta-5 and V-beta-11 in I-E-expressing mice, and do not undergo deletion of V-beta-6- and V-beta-8.1-expressing T cells in Mls-1a-positive mice. They are also unaffected by positive selection of V-beta-17a+ T cells in the context of I-A(q). The results suggest that most selection events require the participation of CD4 and CD8, while alpha/beta-DN cells are unselected. This argues that most alpha/beta-DN cells probably have never expressed CD4 or CD8. However, a unique form of repertoire selection occurs: enrichment of V-beta-17a+ alpha/beta-DN cells in I-E+ mice. This could be an instance of coreceptor-independent selection.