Interactions between MHC-encoded products and cloned T-cells. I. Fine specificity of induction of proliferation and lysis.

To study the interactions between T cells and class I MHC products, we developed in vitro a T-cell line reactive to H-2Kb stimulating cells and derived T-cell clones from it. Although the T-cell line could proliferate in the absence of exogeneous T-cell growth factors when stimulated with H-2Kb spleen cells, each of the derived T-cell clones required both H-2Kb stimulating cells and an external source of T-cell growth factor for its propagation. Each of the T-cell clones was also cytolytic for H-2Kb target cells. Such T-cell clones allowed the comparison of the antigenic requirements for proliferation and cytolysis. By using H-2Kb mutant mice, we found that while the original anti-H-2Kb T-cell line reacted with each of the six mutants tested, the individual T-cell clones could be distinguished in terms of their reactivity pattern. Similar fine specificity patterns were found when H-2Kb mutant cells were used as stimulating or target cells for any given T-cell clone. Each of the three monoclonal H-2Kb-specific antibodies reacting with different epitopes of the H-2Kb molecule totally inhibited H-2Kb-induced proliferation and lysis by the T-cell clones. Further blocking studies involved use of Fab antibody fragments and definition of their reactivity on cells from the H-2Kb mutants. We concluded that: (1) blocking with a monoclonal antibody does not prove identity of alloantigens recognized by the T-cells and the antibody; (2) a monoclonal antibody could either block or not block H-2Kb-CTL interactions depending on structural variations of the H-2Kb molecule not affecting the CTL-H-2Kb functional interaction; (3) blocking one type of H-2Kb-T-cell interaction (induction of proliferation) always affects the other type (cytolysis).