POSITIVE SELECTION OF CD4(-CELLS BY TCR-SPECIFIC ANTIBODIES REQUIRES LOW VALENCY TCR CROSS-LINKING - IMPLICATIONS FOR REPERTOIRE SELECTION IN THE THYMUS() T)

The developmental fate of immature CD4(+) 8(+) thymocytes is determine d by intrathymic signals transduced by surface TCR complexes. In parti cular, TCR signals are required for immature CD4(+) 8(+) thymocytes to further differentiate into CD4(+) 8(-) or CD4(-) 8(+) T cells, a proc ess referred to as positive selection. It is generally thought that po sitive selection results from low affinity TCR interactions with self antigens which engage the relatively few surface TCR complexes that ar e on immature CD4(+) 8(+) thymocytes. However, we now demonstrate with TCR-specific antibodies that positive selection of CD4(+) T cells req uires low valency crosslinking of surface TCR complexes on immature th ymocytes. That is, positive selection signals are only generated withi n a narrow range of TCR cross-linking: cross-linking either too few or too many surface TCR complexes fails to signal positive selection. We interpret these results as indicating that positive selection of CD4( +) T cells is not signaled by low affinity TCR interactions per se, bu t rather can be signaled by any combination of TCR affinity and ligand density that induces low valency TCR cross-linking on immature thymoc ytes.