The Lck Paradox: Because of Inconsistent Experimental Evidence, the Role of the Protein Tyrosine Kinase p56lck in Early Thymic Development Remains Poorly Defined

Since this article was written, publications by several groups of investigators shed additional light on the lck paradox: Firstly, as considered in this mini-review, two papers now show that fyn can partially substitute for Ick in pre-T cell receptor dependent proliferation and differentiation. (T. Groves, P. Smiley, M.P. Cooke K. Forbush, R.M. Perlmutter, and C.J. Guidos. (1996). fyn can partially substitute for lck in T lymphocytes development. Immunity 5: 417; N.S.C. van Oers, B. Lowin-Kropf, D. Finlay, K. Connolly, and A. Weiss. (1996). cq3 T cell development is abolished in mice lacking both lck and fyn protein tyrosine kinases. Immunity 5" 429). This work implies that the dominant negative mutant of lck competes with both Ick and fyn and thus partially resolves the lck paradox. Secondly, concerning TCR/3 locus allelic exclusion, it was shown that components of the CD3 complex are necessary for the exclusion of endogenous TCR/3 genes by a rearranged TCR/3 transgene (L. Ardouin, J. Ismaili, B. Malissen, and M. Malissen. (1998) The CD3-y6 and CD3-/7 modules are each essential for allelic exclusion of the T cell receptor/3 locus but are both dispensable for the initiation of V to (D)J recombination at the T cell receptor-/3, -% and -6 loci. J. Exp. Med. 187:5). However, these as well as many previous studies on TCR/3 transgenemediated exclusion of endogenous TCR/3 genes may have been misleading as recent work also suggested that this approach may generate transgenic artefacts (I. Aifantis, J. Buer, H. von Boehmer, and O. Azogui. (1997) Essential role of the pre-T cell receptor in allelic exclusion of the T cell receptor /3 locus. Immunity 7: 601). Since much of the data on the role of lck in TCR/3 allelic exclusion has been generated by this approach, it is possible that such transgenic artefacts have contributed to the inconsistencies concerning the role of lck in TCR/3 locus allelic exclusion.