Structural aspects of chaperone-mediated peptide loading in the MHC-I antigen presentation pathway

Abstract

Recognition of foreign and dysregulated antigens by the cellular innate and adaptive immune systems is in large part dependent on the cell surface display of peptide/MHC (pMHC) complexes. The formation of such complexes requires the generation of antigenic peptides, proper folding of MHC molecules, loading of peptides onto MHC molecules, glycosylation, and transport to the plasma membrane. This complex series of biosynthetic, biochemical, and cell biological reactions is known as “antigen processing and presentation”. Here, we summarize recent work, focused on the structural and functional characterization of the key MHC-I-dedicated chaperones, tapasin, and TAPBPR. The mechanisms reflect the ability of conformationally flexible molecules to adapt to their ligands, and are comparable to similar processes that are exploited in peptide antigen loading in the MHC-II pathway.

Keywords:

• Antigen presenting cell (APC)
• major histocompatibility complex (MHC)
• peptide-loading complex (PLC)
• tapasin
• TAP-binding protein related (TAPBPR)
• X-ray crystallography
• nuclear magnetic resonance spectroscopy (NMR)

Acknowledgements

We thank the members of our laboratory for their help, and accept responsibility for any errors or omissions.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the intramural research program of the NIAID, NIH.