Loss of a key enzyme can substantially alter how the immune system recognizes tissue antigens according to a report in the January 2007 issue of Nature Immunology.
Nilabh Shastri and colleagues took a close look at mice lacking the enzyme called ERAAP, to discover if these mice bore any immunologic defect. ERAAP trims bits of protein that are displayed on cell surfaces by molecules known as major histocompatibility antigens (MHC), which are the tissue-matching antigens doctors use to identify potential organ donors for transplant patients. Essentially, this trimming process is akin to fitting an oversized hot dog into a bun; ERAAP clips the protruding end of the peptide to nestle snugly within the confines of the MHC molecule.
The study shows vigorous immune reactions resulted when researchers mixed cells from ERAAP-deficient mice with those of wild-type mice that express ERAAP protein. These immune responses were as strong as those seen during rejection episodes of MHC-mismatched transplant patients. These results suggest vast differences exist in the collection of peptides presented by the ERAAP-deficient cells as compared to otherwise genetically identical wild-type mice. The authors speculate inhibiting ERAAP function in tumours might enhance their ability to be targeted and destroyed by the immune system, or conversely, spontaneous loss of ERAAP function in otherwise healthy tissues might lead to autoimmune disease.
Nilabh Shastri (University of California Berkeley, CA, USA)
Additional comment on the paper:
Peter Jensen (University of Utah School of Medicine, Salt Lake City, UT, USA)
Abstract available online.
(C) Nature Immunology press release.
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