Phosphorylation of class I MHC molecules in the absence of phorbol esters is an intracellular event and may be characteristic of trafficking molecules.
Class I Major Histocompatibility Complex (MHC) molecules are displayed at the cell surface where they present antigenic peptides to T lymphocytes. Class I MHC molecules undergo cytoplasmic domain phosphorylation on a serine residue late in their biosynthesis. Here we show that phosphorylation occurs on mature, beta(2)-microglobulin-associated class I MHC molecules in a mouse lymphoid cell line. Both recently synthesized class I MHC molecules and molecules which are at least 3 h old become phosphorylated. Approximately 14% of phosphorylated class I MHC molecules occur at the cell surface. Density gradient analysis indicates that phosphorylated class I MHC molecules also occur in lamp(+) intracellular compartments and in fractions containing rab4, a GTP-binding protein associated with recycling endosomes. Class I MHC molecules are endocytosed and recycled to the cell surface in these cells. Furthermore, the lysosomotropic drug, primaquine, inhibits both class I MHC phosphorylation and its recycling back to the cell surface, suggesting that phosphorylation is related to class I MHC recycling. These observations are intriguing since several studies have shown that class I MHC molecules can acquire antigenic peptides in NH(4)Cl-sensitive compartments. Hence, class I MHC phosphorylation may play a role in regulating intracellular sorting through these compartments.
Capps
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Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz, CA 95064, USA.
Zúñiga
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MC
D000818:Animals; D002460:Cell Line; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006596:Hexosaminidases / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D017026:Swainsonine / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin; D006596:Hexosaminidases; D017026:Swainsonine