Constitutive endocytosis of HLA class I antigens requires a specific portion of the intracytoplasmic tail that shares structural features with other endocytosed molecules.
HLA class I antigens present in the human leukemia T-cell line HPB-ALL are shown to be endocytosed in the absence of specific antibodies. In 1 hr, approximately 10% of class I molecules initially present at the cell surface are found intracellularly. Genetically engineered mutants of the HLA-A2 gene lacking exon 6 or 7 or both were used to analyze whether the cytoplasmic region contributes to the internalization. The results indicate that amino acids encoded by exon 7 (spanning amino acid residues 323-340) are required for internalization, while deletion of exon 6 had no effect. In addition, a comparison of the cytoplasmic sequences of receptors that are known to be internalized via coated pits and the present data revealed that they share a structural feature that could constitute a specific signal required for endocytosis.
Vega
M A
MA
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Strominger
J L
JL
D000936:Antigen-Antibody Complex; D003034:Coated Pits, Cell-Membrane / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D004252:DNA Mutational Analysis; D004705:Endocytosis; D015234:HLA-A Antigens / Q000378:metabolism*; D015789:HLA-A2 Antigen; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000936:Antigen-Antibody Complex; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins