ABC transporters in adaptive immunity

Abstract

Background: ABC transporters ubiquitously found in all kingdoms of life move a broad range of solutes across membranes. Crystal structures of four distinct types of ABC transport systems have been solved, shedding light on different conformational states within the transport process. Briefly, ATP-dependent flipping between inward- and outward-facing conformations allows directional transport of various solutes.

Scope of review: The heterodimeric transporter associated with antigen processing TAP1/2 (ABCB2/3) is a crucial element of the adaptive immune system. The ABC transport complex shuttles proteasomal degradation products into the endoplasmic reticulum. These antigenic peptides are loaded onto major histocompatibility complex class I molecules and presented on the cell surface. We detail the functional modules of TAP, its ATPase and transport cycle, and its interaction with and modulation by other cellular components. In particular, we emphasize how viral factors inhibit TAP activity and thereby prevent detection of the infected host cell by cytotoxic T-cells.

Major conclusions: Merging functional details on TAP with structural insights from related ABC transporters refines the understanding of solute transport. Although human ABC transporters are extremely diverse, they still may employ conceptually related transport mechanisms. Appropriately, we delineate a working model of the transport cycle and how viral factors arrest TAP in distinct conformations.

General significance: Deciphering the transport cycle of human ABC proteins is the major issue in the field. The defined peptidic substrate, various inhibitory viral factors, and its role in adaptive immunity provide unique tools for the investigation of TAP, making it an ideal model system for ABC transporters in general. This article is part of a Special Issue entitled Structural biochemistry and biophysics of membrane proteins.

Keywords: ABC protein; Antigen processing; Membrane proteins; Transport ATPases; Transporter associated with antigen processing; Viral immune escape.