Function of the Antigen Transport Complex TAP in Cellular Immunity

Abstract

The immune system consists of several kinds of cells and molecules whose complex interactions form an efficient system for the protection of an individual from outside invaders and its own transformed cells. Innate immunity refers to the immediate antimicrobial response that occurs regardless of the nature of the invader. The adaptive immune system, on the other hand, mounts specialized immune responses to protect the individual against foreign cells from specific invaders or even tumorigenic cells, and provides long-term protection from subsequent exposure to these foreign cells. Antibody production and cell-mediated responses are the two interconnected branches of the adaptive immune system. Antigenic peptides displayed on the cell surface usually activate the cellular immune response. The transporter associated with antigen processing (TAP) plays a key role in the peptide-processing and -presentation pathway. This Review discusses the latest progress in the structure and mechanism as well as the diseases arising from dysfunction of the TAP complex.

TAP1 and TAP2 polymorphisms associated with ankylosing spondylitis in genetically homogenous Chinese Han population

“…The ABC transport NBD is hydrophilic and highly conserved. It binds ATP, which provides the energy necessary for TAP to transport the degradation antigen peptide to endoplasmic reticulum [22]. SNP variation in either of these two sites likely changes the structure and influences the antigen peptide transport process.…”

Design, synthesis and evaluation of β-lactam antigenic peptide hybrids; unusual opening of the β-lactam ring in acidic media

“…Tumor-associated APs, usually 8 to 10 amino acids long, 6 are generated in cancer cells by proteolysis of self over-expressed proteins in the proteasome and are then exposed to the cell surface by class-I major histocompatibility (MHC-I) complexes to be screened by circulating CD8 + cytotoxic T lymphocytes. 7 Recognition of these peptide-MHC-I (pMHC-I) complexes by T cell receptors (TCRs) is the causal event in the triggering of T cell-mediated immune responses that result in the destruction of antigen-presenting cells. Given the pivotal role played by APs in launching this cellular defense mechanism, it is not surprising that these small peptides have been considered by immunologists as promising leads in the development of immunotherapeutic drugs, as well as synthetic vaccines.…”

Hydrophobic Interactions Are Key To Drive the Association of Tapasin with Peptide Transporter Subunit TAP2

“…These are then translocated into the endoplasmic reticulum (ER) by the transporter associated with Ag processing (TAP) and loaded onto MHC I molecules in the so-called peptideloading complex (PLC) (3). The function of the PLC is to facilitate the transfer of peptide Ags, typically 8-11 aa long, into the peptide-binding groove of MHC I and to edit the respective peptide repertoire in a way that only high-affinity ligands are loaded (4). Once MHC I has captured an appropriate peptide ligand, it dissociates from the PLC and migrates via the exocytic pathway to the plasma membrane (5).…”

“…Once MHC I has captured an appropriate peptide ligand, it dissociates from the PLC and migrates via the exocytic pathway to the plasma membrane (5). TAP is a member of the ATP-binding cassette transporter family (4) and forms a heterodimer consisting of two subunits, TAP1 and TAP2. Both TAP subunits have a similar domain structure that can be subdivided into an N-terminal transmembrane domain (TMD), which forms the translocation pore within the ER membrane, and a cytosolic C-terminal nucleotide-binding domain, which energizes peptide translocation (6).…”