Internalization of human T lymphocyte receptors.
Monoclonal antibodies specific to human T lymphocyte receptors are currently being used to define the biochemical structure of these proteins as well as of functionally distinct cell subsets. Since one of the antibodies (OKT3) recognizing the T3 (CD3) receptor mimics vital physiological processes involved in the activation of the immune system and has been successfully used as a therapeutical agent, we investigated one of the mechanisms underlying this antibody-receptor interaction. Our results show that after binding of OKT3, the complex (OKT3-T3) disappears rapidly from the cell surface. Using electron microscopy, we found that this down-regulation is due to the internalization of the complex. Parallel experiments performed on the T11 (CD2) and T4 (CD4)/AIDS retrovirus receptor indicate that the same mechanism applies for the down-regulation of those molecules. These data suggest that the T3, T11 and T4 receptors have a behavior comparable to other well characterized, hormonal and viral receptors; they provide information on the metabolization pathway of surface receptors and on the possible intracellular penetration of ligands like the HTLV-III/LAV agent in human T lymphocytes.
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D002738:Chloroquine / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D017977:Deltaretrovirus / Q000378:metabolism; D004705:Endocytosis; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure*; D006377:T-Lymphocytes, Helper-Inducer / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D011991:Receptors, Virus; D002738:Chloroquine; D008985:Monensin