THYMIC SELECTION OF CYTOTOXIC T-CELLS INDEPENDENT OF CD8-ALPHA-LCK ASSOCIATION

The CD8alpha cytoplasmic domain associates with p56lck, a nonreceptor protein-tyrosine kinase. The biological relevance of CD8alpha-Lck asso ciation in T cell development was tested with transgenic mice generate d to express a CD8alpha molecule with two amino acid substitutions in its cytoplasmic domain, which abolishes the association of CD8alpha wi th Lck. The CD8alpha mutant was analyzed in a CD8-/- background and in the context of the transgenic 2C T cell receptor. The development and function of CD8+ T cells in these mice were apparently normal. Thus, CD8alpha-Lck association is not necessary for positive selection, nega tive selection, or CD8-dependent cytotoxic function.