Mimicking nickel allergy

An allergy to nickel (Ni²⁺) is one of the most common forms of contact dermatitis, but how T cells recognize Ni²⁺-haptenized peptides is unclear. In the Proceedings of the National Academy of Sciences, Dai and colleagues use structural insights obtained with ANi2.3, a Ni²⁺-reactive T cell antigen receptor (TCR), to shed light on the basis of Ni²⁺ allergy. ANi2.3 recognizes an unknown Ni²⁺-haptenized peptide in the context of HLA-DR52c. Their screen fails to identify the Ni²⁺-haptenized peptide recognized by ANi2.3, probably because of low abundance of the natural ligand. However, it identifies many 'mimetopes' recognized by ANi2.3 in the absence of Ni²⁺. Structural and mutational analysis of the mimetope-DR52c complex shows a highly conserved lysine at peptide position 7 that is essential for recognition by ANi2.3. The e-amino group of this lysine interacts with complementarity-determining region 3 of ANi2.3 in a manner analogous to Ni²⁺, most probably because of its equivalent positive side chains.

Proc. Natl. Acad. Sci. USA 109, 18517–18522 (2012)