MHC CLASS-II REGION ENCODING PROTEINS RELATED TO THE MULTIDRUG RESISTANCE FAMILY OF TRANSMEMBRANE TRANSPORTERS

THE T-cell immune response is directed against antigenic peptide fragments generated in intracellular compartments, the cytosol or the endocytic system1. Peptides derived from cytosolic proteins, usually of biosynthetic origin, are presented efficiently to T-cell receptors by major histocompatibility complex (MHC) class I molecules2-4, with which they assemble, probably in the endoplas-mic reticulum (ER)5. 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 MHC6-8. Here we show that one of these, the rat cim gene6, 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 resistance9,10. Other members of this family of transporter proteins are known to be capable of transporting proteins11,12 and peptides13 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 ER14,15. © 1990 Nature Publishing Group.