A Molecular Map of T Cell Development

Using a sensitive molecular marker for positive selection, the appearance of a particular functional TCR alpha chain sequence in cells from mice bearing a transgenic beta chain, we address several aspects of intrathymic T cell development. First, by examining specific TCR prior to and after maturation, we demonstrate how a restricted TCR repertoire is positively selected from a highly diverse immature TCR repertoire. Second, since this molecular marker is enriched in cells progressing toward the CD4 lineage and depleted in cells progressing toward the CD8 lineage, a map of the developmental pathway of alphabeta thymocytes can be inferred. Third, the first cells that show clear signs of positive intrathymic selection are identified.