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.