T-cell activation. I. Evidence for a functional linkage between class I MHC antigens and the Tc-Ti complex

This paper examines the possibility of a functional linkage between class I MHC molecules and the T-cell receptor complex for antigen (T3-Ti). A newly developed anti-CD3 antibody (500A2) was used as an activation signal for EL4 lymphoma cells and allospecific cytotoxic T-cell clones (CTL), and the production of IL-2/IL-2 receptor in EL4 cells and serine esterase in CTL was determined. Anti-CD3 antibody-induced activation of both EL4 and CTL cells was enhanced in the presence of immunologically cross-linked and immobilized anti-H-2 (class I) antibody reactive against the H-2 haplotype of the responding T cells. A number of H-2-negative and H-2-positive EL4 subclones were generated and tested for anti-CD3 antibody-induced IL-2/IL-2 receptor production. Although both H-2-positive and -negative subclones expressed CD3 antigen and produced IL-2 after activation with the phorbol ester TPA, only the H-2-positive cell clones produced IL-2 and expressed IL-2 receptor after anti-CD3 antibody induction. Our results are compatible with the existence of a functional linkage between the class I and the CD3 molecules on the surface of T cells.