Recipes for cream cakes often go down through Norwegian families. The exact combination of filling and decoration can vary substantially from family to family. But no one is ever in doubt that the result is cream cake, nor that the cake looks yummy.

Likewise there are some genes that exist in countless variations in the population. But every one of us has only inherited two varieties of each such gene, one from our father and one from our mother. The variants of any such diverse (polymorphic) gene all give the recipe for a given protein in the body, although the resulting molecules may vary widely.

By far the most polymorphic genes we have are the HLA genes. HLA molecules are crucial for the immune system to react to unknown threats such as microbes and cancer cells.

Different HLA molecules bind different sets of peptides

There are over 3,000 different varieties of the HLA-B gene, and also for the other five HLA genes (A, C, DR, DQ and DP) there are very many variants known so far. Almost all the differences between the variants of each HLA molecule are localized to the groove. The groove is the part of the molecule that can bind and show off foreign substances to the immune cells. The groove has room to accommodate a peptide, that is a short piece of a protein. The shape and structure of the groove determines which peptides that can bind to it. Each particular groove can bind a great number of different but similar peptides. However, for each groove there will be many peptides that can not bind.

This means that since each of us is equipped with a limited number of HLA molecules, we also have a limited ability to bind and present peptides from microbes and cancer cells to our immune cells. This may have consequences for our chances of survival in an epidemy, if the bacterium or the virus have peptides that only binds well to some but not all HLA molecules. But generally the set of HLA molecules that each of us are equipped with, is adequate for surviving most of the infections we may experience.

Thus in the same way as the Norwegian cream cake serves as party food or dessert almost irrespective of any choice of decoration and filling, so do our HLA molecules serve well as defense against almost any virus or bacteria that we are exposed to.

It is not possible to foresee whether an HLA molecule is especially “good” or “bad”, it depends on the microbes we are exposed to through our lifetime. Neither is it easy to know which cream cake will prevail in the weekly magazine’s cake competition. Which variant will have the strongest appeal at any given time? A layered cream sponge decorated with wafer biscuits for example?

The fact that each of us has a limited number of HLA molecules is the result of a compromise the immune system has had to do, which I shall come back to in a later blog post. Suffice it to say now that both too few and too many HLA molecules is problematic, just like a festive cake buffet indeed may contain too few or too many different cakes.

Blogpost by Anne Spurkland, first published in Norwegian October 12 2012
English version published August 25 2016