ADVERTISEMENT
ADVERTISEMENT

Drug Allergy in the Pocket

An HIV drug can bind to and alter the function of an immune molecule, causing a dangerous reaction in patients with a particular allele.

kerry grens
Kerry Grens

Kerry served as The Scientist’s news director until 2021. Before joining The Scientist in 2013, she was a stringer for Reuters Health, the senior health and science reporter at...

View full profile.


Learn about our editorial policies.

EDITOR'S CHOICE IN IMMUNOLOGY

The paper

D.A. Ostrov et al., “Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire,” PNAS, 109:9959-64, 2012.

The problem

The HIV drug abacavir can cause a severe hypersensitivity reaction in 8 percent of patients—those who share the human leukocyte antigen (HLA) allele HLA-B*57:01. HLA proteins present foreign antigens to T cells; they can also bind a set of “self” peptides preselected during development. Anything outside this set is targeted by the immune system as foreign. To determine why patients with HLA-B*57:01 are so hypersensitive, Bjoern Peters of the La Jolla Institute for Allergy and Immunology and colleagues tested which peptides HLA-B*57:01 binds in the absence and presence of abacavir.

The finding

When exposed to abacavir, HLA-B*57:01 binds self peptides it would normally ignore. X-ray crystallography of HLA-B*57:01-peptide complexes revealed why: the drug inserts into and alters a part of the molecule’s peptide-binding cleft...

The others

Nature

The fix

Interested in reading more?

Magaizne Cover

Become a Member of

Receive full access to digital editions of The Scientist, as well as TS Digest, feature stories, more than 35 years of archives, and much more!
Already a member?
ADVERTISEMENT