Mechanism of Thy-1-mediated T cell activation: roles of Fc receptors, T200, Ia, and H-2 glycoproteins in accessory cell function.

Abstract

Abstract The activation ligand and the molecular and cellular requirements for accessory cell function in murine T cell activation initiated by rabbit anti-Thy-1 antibodies were examined. Both rabbit anti-mouse brain (RaMB) and anti-Thy-1 glycoprotein antibodies initiated T lymphocyte proliferation and precipitated a unique 25,000-dalton glycoprotein after absorption with S49 Thy-1− but not with S49 Thy-1+ T lymphoma cell lines, suggesting that the Thy-1 glycoprotein shares at least a portion of the activation determinant. Antibodies directed against the allodeterminants (Thy-1.1, 1.2) were neither mitogenic or inhibitory to rabbit anti-Thy-1-induced responses. Since rat Thy-1-bearing tissue was effective in absorbing mitogenic activity, it was concluded that the activation ligand was composed of at least 1 rat-mouse shared determinant and possibly an additional mouse-specific determinant(s). The accessory cell requirement was examined by comparing the ability of a number of cell populations to provide helper activity when added to cultures of purified lymph node T lymphocytes pretreated with RaMB. With the exception of peritoneal macrophages, a variety of Fc receptor-(FcR) positive cell types supplied accessory cell function, including B cells, T cells, and macrophages. Helper cell effects were abrogated by UV or glutaralde-hyde treatment, suggesting a requirement for membrane mobility. Accessory cells were not required if aggregation of the RaMB-Thy-1 complex was initiated by anti-lg cross-linking in the absence of helper cells. The hypothesis that the co-redistribution of the FcR-anti-Thy-1 complex involves other membrane proteins in the plasma membrane was tested using monoclonal antibodies directed against H-2, la, and T200 glycoproteins. Anti-H-2K and anti-H-2D, anti-T200, and anti-la antibodies inhibited activation of spleen cells by RaMB but did not affect Con A-, PHA-, or LPS-induced proliferative responses. Antibody pretreatment and genetic evidence strongly favored the conclusion that inhibition by anti-H-2 and anti-T200 antibodies was directed through the accessory cell rather than the responding T cell. It is postulated that transmembrane mobility of these components and/or the FcR on the accessory cell is in some way compromised by these antibodies.