Differential Involvement of Protein Tyrosine Kinases p56^lck and p59^fyn in T Cell Development

Abstract

Mature CD4⁺ and CD8⁺ T cells recognize and respond to processed antigens associated with major histocompatibility complex-encoded molecules (MHC). It is during thymic development that selection processes act on immature CD4⁺CD8⁺ thymocytes to ensure the fonnation of a repertoire of functional T cells^1,2. Thus, immature T cells expressing an ∝β TCR with specificity for self-peptides plus MHC class I or class II molecules are positively selected, differentiating into CD8⁺ or CD4⁺ T cells, respectively^3,4,5,6. Immature thymocytes lacking or expressing a non-selectable TCR undergo programmed cell death¹. Additionally, those CD4⁺CD8⁺ T cells expressing an autospecific TCR may undergo programmed cell death ^7,8 (negative selection). The CD4 and CD8 molecules are thought to actively participate in these T cell repertoire selection events through their coreceptor functions⁹. In a coreceptor model, the TCR and appropriate coreceptor molecule recognize and interact with the same MHC molecule, with CD4 or CD8 potentiating TCR-derived intracellular signals^10,1l.12. Recent reports have demonstrated that mutations affecting CD8/class I MHC interactions disrupt both positive and negative selection in the thymus^13,14.