In 2011, Norwegian researchers published in Nature, one of the world’s most prestigious journals, a map of the cod’s genes. The cod is “ours”. For centuries it has given livelihood for people along the entire Norwegian coastline, including my own grandfather that exported salted, dried cod to Portugal and Brazil. It was therefore a big surprise when the researchers discovered that the cod lacks genes for HLA class II molecules. How can the cod do without something that is so crucial for the immune system in humans and mice?

HLA -molecules are necessary for T cells to discover and react to foreign substances both within, and surrounding the body’s cells. There are therefore two types of HLA-molecules, class I and class II. Class I molecules present peptides from the cells’ inner environment, while class II molecules present peptides from the cells’ external environment.

HLA class I molecules are found on the surface of all cells of the body, and are necessary for T-killer cells to detect virus infected cells. HLA class II molecules, in contrast, are only found on antigen presenting cells. These cells can pick up and present foreign substances (or antigens) to the T helper cells. T-helper cells control many of the other immune cells and therefore plays a critical role in the immune system.

Macrophages and B cells (which the readers of the blog already have been introduced to) can function as antigen presenting cells. But in particular a third cell type, dendritic cells, are specialized for the task. These cells have long protrusions extending in all directions to capture as much as possible of what is happening in the tissue.


A bacterium is taken up by an antigen presenting cell (1), is broken down and presented in the groove of HLA class II molecules (2) to T-helper cells (3) which are activated (4) and help B-cells (5) to make antibodies against the bacterium (6).

When a bacteria or a virus come into the body, the microbe will sooner or later be picked up by an antigen presenting cell, taken into the cell and digested to smaller components. Instead of digesting everything down to the particular building blocks, antigen-presenting cells will keep some bits and pieces of the proteins. These bits, or peptides, will be loaded onto the groove of HLA class II molecules and transported out to the surface of the cells. Passing T helper cells with receptors that can recognize the given combination of HLA-molecule and peptide will be stimulated to react. This will make the helper cells start to send out signal substances that inform the other immune cells (for instance the B cells) about what further action is needed to get rid of the current microbe.

The HIV/AIDS epidemics illustrate well the importance of HLA class II molecules and T helper cells. HIV infect the T helper cells. Without treatment, the T helper cells will gradually disappear, and the patients will die from infections they would normally have survived.

So how does the cod manage without the HLA class II molecules? Molecules that we think are crucial for the intricate system with T helper cells as the director of large part of the immune defense. We still do not have a good answer to this conundrum.

In the meantime, we still export dried cod to Portugal, where it is called baccalao. Baccalao is served in numerous different ways, with or without tomato sauce, and without anyone, even a single moment, being concerned that the fish from Norway lacks HLA-class II molecules.

Blog post by Anne Spurkland, published 23th November 2018
Originally published in Norwegian, 22.10.2012

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