ORIGIN OF A T-CELL CLONE WITH A MISMATCHED COMBINATION OF MHC RESTRICTION AND CORECEPTOR EXPRESSION

Although the existence of a large number of CD8(+) class II MHC-specif ic CTLs has long been noticed, the origin of such T cells with a disco rdant combination of specificity and phenotype has been a mystery in t he positive selection model. Recent reports suggesting the independenc y of the positive selection of T cells from coreceptor-mediated signal s raised a possibility that they might be the progeny of putative tran sitional, mismatched, single-positive cells appearing before positive selection as proposed in the stochastic/selective model. By developing transgenic mice carrying TCR alpha and beta chain genes of a CD8(+) c lass II MHC Ag-specific allogeneic CTL clone QM11, the origin of such T cells with mismatched TCR specificity and coreceptor expression was studied. The results indicate that QM11 belongs to a conventional CD8( +) T cell population whose maturation is dependent on a class I (or cl ass I-like) MHC product. Consequently, the reactivity of QM11 to I-A(k ) can be considered to be an accidental cross-reaction.