PROGRAMMING FOR RECOGNITION AND PROGRAMMING FOR RESPONSE - SEPARATE DEVELOPMENTAL SUBROUTINES IN THE MURINE THYMUS

Pre-T cells become programmed with the capacity to make functional res ponses to activating stimuli in a process that occurs prior to, and in dependently of, T-cell receptor gene rearrangement and T-cell receptor -dependent positive selection. In spite of this early programming, as differentiation proceeds further the cells enter a stage in which they appear to be unable to make any functional responses. This 'eclipse' phase begins when the cells undergo successful T-cell receptor beta-ch ain rearrangement and ends, with the return of their functional compet ence, only when they successfully traverse positive selection. These r esults suggest that pre-T cells are subject to two distinct subroutine s of differentiation, which cannot operate at the same time: one which confers function and one which confers and selects recognition specif icity. To provide a possible molecular basis for the relationship betw een these two processes, we consider specific alterations in response- associated transcription factors that may cause the changes in respons iveness observed during programming for recognition. The interplay of the two differentiation subroutines is proposed to be a consequence of the use of common transcription factors in different combinatorial co ntexts for functional responses, assembly of T-cell receptor complexes , and selection.