Abstract
Besides having physiological functions and general toxic effects, many metal ions can cause allergic reactions in humans. We here review the immune events involved in the mediation of metal allergies. We focus on nickel (Ni), cobalt (Co) and palladium (Pd), because these allergens are among the most prevalent sensitizers (Ni, Co) and immediate neighbors in the periodic table of the chemical elements. Co-sensitization between Ni and the other two metals is frequent while the knowledge on a possible immunological cross-reactivity using in vivo and in vitro approaches remains limited. At the center of an allergic reaction lies the capability of a metal allergen to form T cell epitopes that are recognized by specific T cell receptors (TCR). Technological advances such as activation-induced marker assays and TCR high-throughput sequencing recently provided new insights into the interaction of Ni2+ with the αβ TCR-peptide-major histocompatibility complex (pMHC) interface. Ni2+ functionally binds to the TCR gene segment TRAV9-2 or a histidine in the complementarity determining region 3 (CDR3), the main antigen binding region. Thus, we overview known, newly identified and hypothesized mechanisms of metal-specific T cell activation and discuss current knowledge on cross-reactivity.
Highlights
Metals are present in many areas of industrialized life
We focus on Ni because it is the most common identified in vivo inis vitro studies.literature
Experimental evidence hashas been obtained forfor fivefive different interactions between thethe cell receptor (TCR), the metal ion and the peptide presented at the surface of the major histocomcell receptor (TCR), the metal ion and the peptide presented at the surface of the major histocompatibility patibility complex (A)ion
Summary
Metals are present in many areas of industrialized life. People are exposed to metals through the environment, consumer products, workplaces and medical appliances such as implants or drugs. A multitude of metallic elements has been associated with allergic reactions, among them nickel (Ni, Ni2+ ions), cobalt (Co, Co2+ ions) and palladium (Pd, Pd2+ ions) (Figure 1) [4,5,6]. Metal allergens may interact with both the innate and adaptive immune system. Concerning the latter, the underlying mechanisms of allergic reactions include the formation of allergen-induced T cell epitopes recognized by specific T cell receptors (TCR) [7,8]. Since reactive chemicals are too small to be recognized by TCR or antibodies, binding to self-proteins by a process called “haptenization” is mandatory for the interaction with the adaptive immune system [9]. Chemical allergies can be viewed as misguided adaptive immune responses to otherwise relatively harmless chemical exposures.
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