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Comment
. 2020 May 22;295(21):7211-7212.
doi: 10.1074/jbc.H120.013868.

How a tailor achieves the perfect fit

Jeff D Colbert  1 , Kenneth L Rock  2
Affiliations
Comment

How a tailor achieves the perfect fit

Jeff D Colbert et al. J Biol Chem. .

Abstract

Most antigenic peptides that bind stably to a major histocompatibility complex (MHC) I molecule for display to the immune system are approximately the same length, thanks in part to the expert trimming done by endoplasmic reticulum aminopeptidases (ERAPs), the final peptidases in the antigen-presentation pathway. An open question is whether ERAPs edit peptides to this optimal length while they are bound to MHC I molecules (using the latter as a pattern of sorts) or by free hand. Mavridis et al. present multiple lines of evidence that this trimming cannot readily occur on MHC I molecules, but rather only in solution, suggesting that ERAPs work alone to tailor the perfect fit for the immunopeptidome.

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Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article

Figures

Figure 1.
Figure 1.
Models for ERAP generation of MHC I–presented peptides. Top, ERAP1 trimming of long peptides to mature (optimal) size in solution, followed by peptide binding to MHC I molecules. Bottom, using MHC I molecules as a size template for ERAP to trim MHC I–bound long peptides to mature size. The dashed arrows indicate that this pathway is unlikely, based on results from Mavridis et al. (8).
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References

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