The cytoplasmic tail of CD4 targets chimeric molecules to a degradative pathway.
Many different cell surface receptors undergo endocytosis via coated pits. Once having entered the cell, the receptors are sorted into diverse pathways. Which path a given receptor will follow is determined by signals inherent in the receptor's structure. The nature of these structural features is not yet known. In this study, we have taken the approach of constructing chimeric molecules to localize the domain of the T-cell surface molecule CD4 which is responsible for targeting it for degradation. Chimeric molecules bearing the cytoplasmic domain of CD4 and the extracellular domain of either the low-density lipoprotein receptor or a major histocompatibility complex (MHC) class I molecule were both internalized in response to phorbol 12-myristate 13-acetate and were subsequently degraded, indicating that the cytoplasmic tail of CD4 contains all the information required for both processes. The ability to modulate the level of MHC class I molecules on the cell surface offers an approach to investigating quantitative aspects of antigen presentation, the initial possibilities of which are explored herein.
Baenziger
J W
JW
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143.
Okamoto
A
A
Hall
E
E
Verma
S
S
Davis
C G
CG
D015704:CD4 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D002678:Chimera; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D015234:HLA-A Antigens / Q000276:immunology; D000922:Immunotoxins; D066298:In Vitro Techniques; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D010957:Plasmids; D011973:Receptors, LDL / Q000276:immunology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D015704:CD4 Antigens; D015234:HLA-A Antigens; D000922:Immunotoxins; D011973:Receptors, LDL; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate