Engagement of class I major histocompatibility complex molecules by cell surface CD8 delivers an activation signal

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Abstract
Recent evidence has demonstrated that cross‐linking class I major histocompatibility complex (MHC) molecules on human T cells with monoclonal antibodies (mAb) triggers T cell activation. The only known natural ligand for MHC class I molecules is CD8.Therefore, the possibility that CD8+ T cells might provide activation signals to other T cells by engaging MHC class I molecules was examined by culturing CD4+ peripheral blood T cells with Chinese hamster ovary cells (CHO) cells that had been transfected with the α chain or α and β chains of CD8 and assessing interleukin (IL)‐2 production. CD4+ T cells did not secrete IL‐2 when cultured alone, with control or CD8+ CHO cells. In contrast, CD4+ T cells produced IL‐2 when cultured with CD8+ CHO cells and co‐stimulated with phorbol myristate acetate (PMA) or mAb to CD3 or CD28. PMA stimulated substantially less IL‐2 when control CHO cells were employed and the mAb to CD3 and CD28 did not stimulate IL‐2 production in the presence of control CHO cells. The co‐stimulatory activity of CD8+CHO cells was completelyeliminated by mAb to CD8 or MHC class I molecules. The data demonstrate that CD8 can interact with MHC class I molecules expressed on T cells and deliver a costimulatory signal that increases IL‐2 production. Thus, engagement of MHC class I molecules byits natural ligand, CD8, provides an activation signal to T cells. Under some circumstances, such interactions may amplify the responses of T cells.