8.A.196. The Tapasin (Tapasin) Family
Tapasin is a component of the antigen processing and presentation pathway, which binds to MHC class I coupled with beta2-microglobulin/B2M. Association between TAPBPR and MHC class I occurs in the absence of a functional peptide-loading complex (PLC). The loading of newly synthesised MHC class I molecules (MHCI) with peptides requires the involvement of several endoplasmic reticulum (ER)-resident cofactors including calnexin (TC# 8.A.165), calreticulin (TC# 8.A.197), transporter associated with antigen processing, ERp57 (TC# 8.A.88.2.7) and tapasin. In the absence of tapasin, MHC I complexes are loaded with suboptimal peptides and their recognition by cytotoxic T cells raised to high-affinity, immunodominant peptide epitopes is impaired (Gao et al. 2004).
Major histocompatibility complex encoded class I (MHC-I) molecules bind a broad spectrum of peptides generated in the cytoplasm and encountered during protein folding and maturation in the ER. For cell surface expression and recognition by T cell receptors (TCR) and natural killer (NK) receptors, MHC-I requires loading with high affinity peptides. Peptide optimization is catalyzed by either of two pathways (Margulies et al. 2020). The first is via the peptide-loading complex (PLC) which consists of the transporter associated with antigen processing (TAP)1/TAP2 heterodimer, tapasin (an ER resident chaperone, also known as TAP-binding protein (TAPBP)), ERp57 (an oxidoreductase TC# 8.A.88.2.7), and calreticulin (a sugar-binding chaperone; TC# 8.A.197). The second pathway depends on TAP-binding protein, related (TAPBPR), a PLC-independent chaperone, that is similar in amino acid sequence and structure to tapasin. Margulies et al. 2020 review recent functional, structural, and computational dynamic studies of tapasin and TAPBPR that contribute to a vivid description of the molecular changes in MHC-I molecules that accompany tapasin or TAPBPR interaction.