Mechanisms of immunosensitization to metals (IUPAC Technical Report)
D. M. Templeton*
Abstract: A project
is underway within IUPAC to evaluate and harmonize the use of various
biomarkers for immunosensitization to metals. This present review summarizes
our knowledge of the mechanisms by which certain trace elements evoke
allergenicity. Some physiological electrolytes (e.g., Na+,
K+) and macronutrients (e.g., Ca2+, Fe3+)
are immunologically inactive. However, some trace elements essential
for cell function (e.g., Co2+, Cu2+, Cr3+),
as well as nonessential elements generally considered toxic (e.g., Hg
species) or in use as therapeutic agents (e.g., some species of Pt and
Au), can give rise to adverse immune reactions. Specific immunological
responses to Ni, Co, Cr, Hg, Be, Cu, Pt, Pd, Ir, In, and Au are discussed.
In general, these elements can activate T or B cells by specific receptor
interactions, resulting in clonal expansion of a metal-specific lymphocyte
and an immune response (typically dermatitis) upon re-exposure. Compelling
evidence points to the primary role of the T cell in responding to the
metal. T-cell activation occurs when a protein of the major histocompatibility
complex (MHC) binds to a T-cell receptor in the presence of an MHC binding
peptide. Many antigenic substances result in presentation of MHC bound
antigenic peptides to the T-cell receptor; metal ions appear to act
as haptens that directly or indirectly cause structural changes in MHC
molecule-peptide complexes that result in recognition of these complexes
by specific T-cell subsets. Nickel and gold are particularly instructive
in understanding mechanisms, and are used to discuss models in which
the metal may bind to the antigenic peptide (i) before or (ii) after
its association with the MHC/T-cell receptor complex, (iii) may bind
to the MHC/receptor complex prior to recruitment of the antigenic peptide,
or (iv) may bind to the formed peptide/MHC/receptor complex through
ligands contributed by one or more of the components.
* Corresponding author.
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