Lck activity controls CD4/CD8 T cell lineage commitment

Thymocytes carrying MHC class I-restricted TCRs differentiate into dos T ce lls, while those recognizing MHC class II become CD4 T cells. The mechanism s underlying how MHC class recognition, coreceptor expression, and effector function are coordinated are not well understood. Since the tyrosine kinas e Lck binds with more affinity to CD4 than CD8, it has been proposed as a c andidate to mediate this process. By using transgenic mice with altered Lck activity, we show that thymocytes carrying a class Ii-restricted TCR devel op into functional CD8 T cells when Lck activity is reduced. Conversely, th ymocytes carrying a class I-restricted TCR develop into functional CD4 T ce lls when Lck activity is increased. these results directly show that quanti tative differences in the Lck signal control the CD4/CD8 lineage decision.