Allelic exclusion in pT alpha-deficient mice: No evidence for cell surface expression of two 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 distinct T cell receptor (TCR)-beta chains, they usually express only one allele, a phenomenon termed allelic exclusion. Expression of a functional TCR-beta chain during early T cell development leads to the formation of a pre-T cell receptor (pre-TCR) complex and, at the same developmental stage, arrest of further TCR-beta rearrangements, suggesting a role of the pre-TCR in mediating allelic exclusion. To investigate the potential link between pre-TCR formation and inhibition of further TCR-beta rearrangements, we have studied the efficiency of allelic exclusion in mice lacking the pre-TCR-alpha (pT alpha) chain, a core component of the pre-TCR. Staining of CD3(+) thymocytes and lymph node cells with antibodies specific for V beta 6 or V beta 8 and a pool of antibodies 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 functionally rearranged TCR-beta transgene. Interestingly, although the transgenic TCR-beta chain significantly influenced thymocyte development even in the absence of pT alpha, it was not able to inhibit fully endogeneous TCR-beta rearrangements either in total thymocytes or in sorted CD25(+) pre-T cells of pT alpha(-/-) mice, clearly indicating an involvement of the pre-TCR in allelic exclusion.