Location of MHC-encoded transporters in the endoplasmic reticulum and cis-Golgi

MJ Kleijmeer, A Kelly, HJ Geuze, JW Slot, A Townsend… - Nature, 1992 - nature.com
MJ Kleijmeer, A Kelly, HJ Geuze, JW Slot, A Townsend, J Trowsdale
Nature, 1992nature.com
IMMUNE recognition of intracellular proteins is mediated by major histocompatibility
complex (MHC) class I molecules that present short peptides to cytotoxic T cells1–4.
Evidence suggests that peptides arise by cleavage of proteins in the cytoplasm and are
transported by a signal-independent mechanism into a pre-Golgi region of the cell, where
they take part in the assembly of class I heavy chains with β2-microglobulin (reviewed in refs
5–7). Analysis of cells that have defects in class I molecule assembly and antigen …
Abstract
IMMUNE recognition of intracellular proteins is mediated by major histocompatibility complex (MHC) class I molecules that present short peptides to cytotoxic T cells1–4. Evidence suggests that peptides arise by cleavage of proteins in the cytoplasm and are transported by a signal-independent mechanism into a pre-Golgi region of the cell, where they take part in the assembly of class I heavy chains with β2-microglobulin (reviewed in refs 5–7). Analysis of cells that have defects in class I molecule assembly and antigen presentation8–14 has shown that this phenotype can result from mutations in either of the two ABC transporter genes located in the class II region of the MHC15–22. This suggested that the protein complex encoded by these two genes20,22 transports peptides from the cytosol into the endoplasmic reticulum. Here we report additional evidence by showing that the transporter complex is located in the endoplasmic reticulum membrane and is probably oriented with its ATP-binding domains in the cytosol.
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