Phosphorylation of class I MHC molecules in the absence of phorbol esters is an intracellular event and may be characteristic of trafficking molecules

Mol Immunol. Jan-Feb 2000;37(1-2):59-71. doi: 10.1016/s0161-5890(00)00019-5.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Endocytosis
  • Endosomes / metabolism
  • Hexosaminidases / pharmacology
  • Histocompatibility Antigens Class I / metabolism*
  • Mice
  • Phosphorylation
  • Swainsonine / pharmacology
  • beta 2-Microglobulin / metabolism

Substances

  • Histocompatibility Antigens Class I
  • beta 2-Microglobulin
  • Hexosaminidases
  • Swainsonine