Conceptually, its not excessively hard to understand how we develop allergies– Our bodies generate an inappropriate immune response to a protein that wouldnt otherwise cause us any harm, whether its tree pollen or dust mites or peanut proteins.
Nickel is a cation– Ni2+. Our bodies are chock full of cations– calcium, iron, magnesium, etc, and they dont cause any trouble (or youd be dead). And there are lots of other cations that dont hurt anyone (aluminum, silver, etc). Why Nickel?
Plus, Nickel is a metal. Its not a chunk of a protein, its a metal. How the hell does that work???
Why, apparently its a side-effect of evolution!
One of the ways our bodies defend themselves against pathogens is through pattern recognition. Your body *knows* some things aint right, like double-stranded RNA (that just shouldnt be anywhere) or certain patterns in sugars or non-methylated DNA, things humans just dont make. When they see these things that aint right, they release all kinds of pro-inflammatory messengers to get the big guns, the actual immune cells, to pay attention to them.
Turns out Nickel loves to snuggle up to TLR-4. There are a series of three histidines that just plain love Nickel. When Nickel binds, it sets off a similar pro-inflammatory immune response that a chunk of bacterial guts would (in the case of an appropriate immune response) or dust might guts (in the case of another inappropriate immune response).
This is neat information for people trying to figure out why some people are allergic to Nickel, how we can treat/avoid it, and so on. Its not every piece of the puzzle, but its a neat piece that helps us understand something big (OHHH! Its a duck!).
Its also a piece to another puzzle– Mice are a crappy animal model for Nickel allergies. But TLRs are pretty evolutionarily conserved. wtf? It seems mice do not have those three histidines that Nickel likes. They might have evolved in humans by chance (neutral mutations) or in response to a specific selective pressure (maybe they were useful for defeating some bacteria humans interacted with)– but they dont have any negative selective pressures against them. Its only in the modern world, where we interact with metals like Nickel all the time, that it results in a negative phenotype!
It also might be a piece to yet another puzzle– We add adjuvants to vaccines. Basically, extra stuff that makes the vaccine work better. You can use different adjuvants to nudge the immune system towards one kind of response, or another, or just to get a nice immune response to the vaccine in the first place. Whats a Big Name adjuvant? Aluminum. We arent exactly sure how it works– maybe through this pathway too?
And then theres still the question I have from the very beginning– Why Nickel? Why not Copper? Zinc? Iron?
Its the best kind of finding– one that answers some questions, and makes you ask a whole bunch more.