Macrophage IA Hybrid Molecule as Product of the Ir-Thy-1 Genes

Abstract

A primary anti-Thy-1 response in mice is under complex genetic control (Zaleski et al. 1986). This control has been shown to involve either class I or class II H-2 molecules depending on the form in which the Thy-1 antigen is presented to a responder. Briefly, when thymocytes from an H-2-compatible donor are used, the cell-bound Thy-1 antigen seems to be presented directly to the responder’s T cells. The latter are believed to require simultaneous stimulation by the carrier-like or helper determinants (Lake and Douglas 1978) or acolytes (Klein and Zaleski 1987). In contrast, when thymocytes from H-2-incompatible donors are used, the cell-free Thy-1 antigen, which is shed from the immunizing thymocytes, appears to be presented by the responder’s macrophages. This presentation most likely involves associative recognition of the Thy-1 antigen and the product of the two complementary Ir-Thy-1 genes (Zaleski and Klein 1978). Recently, it was demonstrated that the product of these genes is identical with a hybrid IA molecule (Quackenbush et al. 1985, Zaleski et al. 1985). The working hypothesis outlined above is based on two crucial observations. First, a good anti-Thy-1 response to the cell-free antigen is demonstrable only in F1 hybrids that express a particular hybrid IA molecule (Quackenbush et al. 1985). Second, in vivo administration of monoclonal antibodies specific for a particular class II molecule inhibits the response to the cell-free, but not to the cell-bound antigen (Zaleski et al. 1985, Quackenbush et al. 1987).