title: Heterologous cross-linking of Lyt-2 (CD8) to the alpha beta-T cell receptor is more effective in T cell activation than homologous alpha beta-T cell receptor cross-linking.
abstract: Ag recognition of Lyt-2 (CD8)-positive T lymphocytes requires the presentation by APC of a suitably processed Ag in association with MHC class I molecules. In previous studies we have obtained evidence that, for optimal activation, both the alpha beta-TCR and Lyt-2 have to participate in this recognition process. In the current study we investigate the functional consequences of limited cross-linking of these cell surface molecules by using soluble, dimeric hetero- and homoconjugates of mAb to Lyt-2 and to the TCR beta-chain (F23.1). Heterologous cross-linking of Lyt-2 to the TCR induced a vigorous, selective Lyt-2+ T cell proliferative response. Functionally active cytotoxic cells were generated, and a high frequency of responding cells was observed in limiting dilution analyses. In contrast, homologous TCR cross-linking initiated a less pronounced proliferation with a relatively low frequency of response, whereas Lyt-2 cross-linking resulted in no cellular proliferation. Significant T cell activation occurred with exposure to anti-Lyt-2: F23.1 mAb dimers at concentrations an order of magnitude lower than those required for stimulation by F23.1:F23.1 mAb dimers. The induction of proliferation by mAb dimers occurred in the absence of Fc components and in rigorously APC depleted, purified T cell preparations. Effective stimulation of resting T cells could be induced also by heterodimers of monovalent Fab fragments. Heterologous cross-linking of Lyt-2 to the TCR was superior to homologous TCR cross-linking primarily with respect to proliferation in IL-2 containing media and to IL-2R expression, whereas proliferation in response to other lymphokines and the production of IL-2 itself were similar under both cross-linking regimens. Thus, when linked to the TCR, Lyt-2 contributed a strong, positive signal toward IL-2-dependent growth of resting T cells. We assume that in the case of Ag-driven T cell activation, the class I MHC molecule acts as the physiologic cross-linking ligand for Lyt-2 and the TCR.
authors.affiliation: Max-Planck-Institut für Immunbiologie, Freiburg, Federal Republic of Germany.
authors.forename: N W
authors.initials: NW
authors.lastname: Boyce
authors.forename: J I
authors.initials: JI
authors.lastname: Jönsson
authors.forename: F
authors.initials: F
authors.lastname: Emmrich
authors.forename: K
authors.initials: K
authors.lastname: Eichmann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D003432:Cross-Linking Reagents; D003602:Cytotoxicity, Immunologic; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis / Q000502:physiology; D007399:Interphase; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000954:Antigens, Surface; D003432:Cross-Linking Reagents; D007376:Interleukin-2; D007378:Interleukins; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4