The prevailing view of thymocyte selection is that the fate of developing cells is dictated exclusively by the affinity/avidity of the expressed TCR for self-MHC/self-ligand. We hypothesize that there is significant plasticity in the signaling processes that control T cell development and that the ability to ‘fine-tune’ the TCR signaling response, through the regulated expression of molecules that positively or negatively impact the TCR signaling response operates to maximize the TCR repertoire. One example of a ‘fine-tuning’ molecule that was previously characterized is the cell surface protein CD5. We found that CD5 is an inhibitory tuning receptor, and its surface expression is directly and proportionately regulated by the affinity of the TCR for selecting ligand. In order to identify additional candidates for ‘TCR-tuning’, we employed a TCR transgenic experimental system where TCR expression was fixed on all developing thymocytes and where the affinity of the positively selecting TCR/self-MHC/self-ligand interaction could be altered by changing the MHC haplotype. Thymocytes that successfully underwent selection under conditions of relatively low or relatively high avidity interactions were analyzed by microarray. These experiments identified CD5 as well as several additional potential tuning molecules not previously thought to play a role in ‘TCR-tuning’. Our results provide important new insights into the genetic and molecular processes that control thymocyte selection.
- Copyright © 2011 by The American Association of Immunologists, Inc.