ASYMMETRIC SIGNALING REQUIREMENTS FOR THYMOCYTE COMMITMENT TO THE CD4(-CELL LINEAGES - A NEW PERSPECTIVE ON THYMIC COMMITMENT AND SELECTION() VERSUS CD8(+) T)

Differentiation of immature CD4(+)CD8(+) thymocytes into mature CD4(+) CD8(-) and CD4(-)CD8(+) T cells requires that synthesis of one or the other coreceptor molecule be terminated, a process referred to as line age commitment. The present study has utilized a novel coreceptor reex pression assay to identify lineage commitment in immature thymocytes a nd has found that the MHC recognition requirements for CD4 commitment and CD8 commitment fundamentally differ from one another. Remarkably, we found that thymocyte commitment to the CD8(+) lineage requires MHC class I-dependent instructional signals, whereas thymocyte commitment to the CD4(+) lineage is MHC independent and may occur by default. In addition, an unanticipated relationship between lineage commitment and surface phenotype has been identified. These results are incompatible with current concepts and require a new perspective on lineage commit ment and positive selection, which we refer to as asymmetric commitmen t.