MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters

Nature. 1990 Dec 20-27;348(6303):738-41. doi: 10.1038/348738a0.

Abstract

The T-cell immune response is directed against antigenic peptide fragments generated in intracellular compartments, the cytosol or the endocytic system. Peptides derived from cytosolic proteins, usually of biosynthetic origin, are presented efficiently to T-cell receptors by major histocompatibility complex (MHC) class I molecules, with which they assemble, probably in the endoplasmic reticulum (ER). In the absence of recognizable N-terminal signal sequences, such cytosolic peptides must be translocated across the ER membrane by a novel mechanism. Genes apparently involved in the normal assembly and transport of class I molecules may themselves be encoded in the MHC. Here we show that one of these, the rat cim gene, maps to a highly polymorphic part of the MHC class II region encoding two novel members of the family of transmembrane transporters related to multidrug resistance. Other members of this family of transporter proteins are known to be capable of transporting proteins and peptides across membranes independently of the classical secretory pathway. Such molecules are credible candidates for peptide pumps that move fragments of antigenic proteins from the cytosol into the ER.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Transport
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • DNA Probes
  • Drug Resistance / genetics*
  • Endoplasmic Reticulum / metabolism
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Polymorphism, Restriction Fragment Length
  • Rats
  • Restriction Mapping

Substances

  • Carrier Proteins
  • DNA Probes
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II