ALLELIC EXCLUSION IN PT-ALPHA-DEFICIENT MICE - NO EVIDENCE FOR CELL-SURFACE EXPRESSION OF 2 T-CELL RECEPTOR (TCR)-BETA CHAINS, BUT LESS EFFICIENT INHIBITION OF ENDOGENEOUS V-BETA-](D)J-BETA REARRANGEMENTS IN THE PRESENCE OF A FUNCTIONAL TCR-BETA TRANSGENE

Although individual T lymphocytes have the potential to generate two d istinct T cell receptor (TCR)-beta chains, they usually express only o ne allele, a phenomenon termed allelic exclusion. Expression of a func tional TCR-beta chain during early T cell development leads to the for mation of a pre-T cell receptor (pre-TCR) complex and, at the same dev elopmental stage, arrest of further TCR-beta rearrangements, suggestin g a role of the pre-TCR in mediating allelic exclusion. To investigate the potential link between pre-TCR formation and inhibition of furthe r TCR-beta rearrangements, we have studied the efficiency of allelic e xclusion in mice lacking the pre-TCR-alpha (pT alpha) chain, a core co mponent of the pre-TCR. Staining of CD3(+) thymocytes and lymph node c ells with antibodies specific for V beta 6 or V beta 8 and a pool of a ntibodies specific for most other V beta elements, did not reveal any violation of allelic exclusion at the level of cell surface expression . This was also true for pT alpha-deficient mice expressing a function ally rearranged TCR-beta transgene. Interestingly, although the transg enic TCR-beta chain significantly influenced thymocyte development eve n in the absence of pT alpha, it was not able to inhibit fully endogen eous TCR-beta rearrangements either in total thymocytes or in sorted C D25(+) pre-T cells of pT alpha(-/-) mice, clearly indicating an involv ement of the pre-TCR in allelic exclusion.