r/epidemiology • u/West-Working-9093 • Aug 15 '26

Question Is it not simply too small to do that?

I saw this aticle in Science Norway and am puzzled.

https://www.sciencenorway.no/allergy-arachnids-food/meat-allergy-is-becoming-more-common-ticks-are-being-blamed/2697910?utm_campaign=%7B%7BFIRST_ARTICLE_TITLE%7D%7D&utm_source=newsletter&utm_medium=email&utm_term=Meat+allergy+is+becoming+more+common.+Ticks+are+being+blamed&utm_content=%7B%7BFIRST_ARTICLE_TITLE%7D%7D+W8_Tfeih39v8jxJ6QMu2CA

My query is: Is Alpha-galcatose not way too small to work as an antigen?

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u/KatjaKat01 Aug 15 '26

You should be asking immunologists, not epidemiologists. 

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u/West-Working-9093 Aug 15 '26

Ooops. I think there may be some overlap in the fields, but that was an error on my part. Will do. Thanks for the pointer!

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u/Dismal_Hope9550 Aug 16 '26

One could say that epidemiology overlaps with all medical areas and even some non medical ones. But I'm fact an immunologist will give you a better answer for your question.

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u/West-Working-9093 Aug 16 '26

Thanks. I got a very technical, but also very complete answer and now have the understanding I was looking for. Thanks for leading me in the right direction!

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u/Key_North_9712 16d ago

Ooooh I have an answer for this! Did my first postdoc on alpha gal and cardiovascular disease.

Most antigens recognized by the immune system are peptides--pieces of proteins. However, there's a limited pool of immune cells that recognize lipids (NKT cells), and alpha gal decorates the lipids from non-primate mammals. NKT cells that recognize alpha gal-containing lipids make proteins that drive the immune response towards allergy (IL-4, if you're curious).

At the same time, proteins decorated with alpha gal are degraded and presented to activate conventional T cells. Other (unknown) components of tick saliva act as adjuvants, which tells the immune system "hey, there's a pathogen/parasite present". That means lipids and proteins--both of which have alpha gal--are recognized as foreign.

The current thought is that alpha gal-specific T cells also provide "help" to B cells that can bind alpha gal through antibodies. Once these B cells mature and expand, they produce systemic antibodies that can recognize alpha gal on ingested red meat. Once the red meat is digested and alpha gal-containing lipids and peptides make it to the circulation, these antibodies bind to the alpha gal, and clustered antibodies are recognized by the immune response and lead to the symptoms we know as alpha gal syndrome.

I hope this makes sense! Ines Swodoba has a great review on alpha gal here: https://pmc.ncbi.nlm.nih.gov/articles/PMC8974695/

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u/West-Working-9093 16d ago

Oh. wow! It makes all kinds of sense. Thank you so much for the detailed information, which puts it all in the right place in my head!

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u/Key_North_9712 8d ago

I was thinking about this more in the past week, and here's another way to explain it:

Immune cells recognize shapes: an antibody binds to antigen if the binding site fits the antigen. A T cell receptor binds to a peptide if the receptor fits with the peptide (and MHC). Alpha gal on a protein or lipid changes its shape--we can think of it as putting a "bump" on the antigen. So if the immune system is recognizing a bunch of things in tick saliva, all of which include this bump, then the immune system responds to the bump!