Losses and Gains

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Science  08 Dec 2006:
Vol. 314, Issue 5805, pp. 1516
DOI: 10.1126/science.314.5805.1516c

Cytotoxic T lymphocytes (CTLs) monitor the body's cells for damage or infection by detecting changes in fragments of proteins presented on the cell surface by major histocompatibility complex (MHC) molecules. The spectrum of peptides presented depends on cellular machinery that chops the proteins into small pieces, and on endoplasmic reticulum aminopeptidases associated with antigen processing (ERAAP), which lop off N-terminal residues to generate peptides of the correct length for binding to MHC complexes.

Hammer et al. show that mice deficient in ERAAP display a large gap in the peptide repertoires presented. However, this hole is filled by a new set of peptides; these peptide-MHC combinations were immunogenic because they stimulated CTL and antibody production by B cells. Nevertheless, the complexes were structurally distinct from those of wild-type cells and appeared unstable because they rapidly disappeared from the cell surface. It will be of interest to investigate the activity of this editing enzyme in situations such as tumor surveillance and viral infection, perhaps with a view to modulating its activity therapeutically. — SJS

Nat. Immunol. 7, 10.1038/ni1409 (2006).

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