Identification and functional characterization of guinea-pig CD4: antibody binding transduces a negative signal on T-cell activation.
The guinea-pig (gp) CD4 protein was identified using the rat monoclonal antibody (mAb) H155 derived from an interspecies hybrid. The hybrid was obtained after immunization of rats with purified guinea-pig T lymphocytes and fusion to a mouse myeloma line. The mAb H155 reacted with a subpopulation (60-70%) of nylon-wool-purified guinea-pig T cells. The majority of thymocytes also expressed the H155 antigen. Immunohistological staining showed that predominantly the cortical thymocytes were H155-positive, whereas a part of the medullary cells did not express the antigen. After cell-surface radioiodination of T cell lines, the mAb H155 immunoprecipitated a molecule of about 55,000 MW both under reducing and non-reducing conditions. The antigen recognized by mAb H155 on guinea-pig T cells resembles the human or mouse CD4 antigen. Depletion experiments in combination with functional studies further supported this assumption. In proliferation assays mAb H155 inhibited T-cell responses in vitro. Both the antigen- and alloantigen-induced T-cell activation were impaired in the continuous presence of mAb H155. In addition, mAb H155 inhibited both the mitogen-induced T-cell activation and T-cell proliferation induced by mitogenic mAb and phorbol myristate acetate (PMA). Binding of the mAb H155 to the CD4 molecule might therefore transduce a negative signal on T-cell activation.
Schäfer
H
H
Department of Immunology, Robert Koch-Institute, BGA, Berlin, Germany.
Burger
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000737:chemistry; D002455:Cell Division / Q000276:immunology; D006168:Guinea Pigs / Q000276:immunology*; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008221:Lymphoid Tissue / Q000276:immunology; D008934:Mitogens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D008934:Mitogens