CD8 T cells from major histocompatibility complex class II‐deficient mice respond vigorously to class II molecules in a primary mixed lymphocyte reaction

Mature CD4+ and CD8+ T cells are restricted by major histocompatibility complex (MHC) class II and class I molecules, respectively. In a primary mixed lymphocyte reaction (MLR), CD8+ T cells from C57BL/6 (B6) mice can respond to allo-class I molecules, but not allo-class II molecules. However, a significant fraction of CD8+ T cells from C57BL/6 class II-deficient (B6Aalpha-) mice violate this rule by responding vigorously in a MLR to class II molecules. The frequency of responding cells is approximately 50% of that of B6 CD8+ T cells responding to B6bm1 allo-class I molecules. This response requires neither appropriate co-receptor, i.e. CD4, nor exogenous lymphokines, indicating that interactions between the T cell receptors (TCR) and class II molecules are remarkably efficient. Since these CD8+ T cells are positively selected by class I molecules in the thymus of class II-deficient mice, these CD8+ T cells should interact with both classes of MHC molecules. The absence of thymic negative selection by class II molecules may result in the production of these CD8+ T cells. The data imply that a substantial fraction of CD4+CD8+ double-positive thymocytes in wild-type mice interacts with both classes of MHC molecules prior to thymic selection.