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

Abstract

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 molecules^2–4, 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 MHC^6–8. 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 resistance^9,10. Other members of this family of transporter proteins are known to be capable of transporting proteins^11,12 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 ER^14,15.