The groove

When my boyfriend finally returned from Africa in 1989, two years of intense letter writing came to an end. I had written about my life as a budding researcher, he about his life as a volunteer in the bush. Still I became a bit puzzled the morning of our reunion in Paris, when he after a night in a cheap hotel bed announced that he had dreamt that we were competing peptides in the HLA groove!

The big question for immunologists in the early 80s was how the immune system’s crucial T cells could “see” foreign substances. The stuff that the immune system can react to is called antigen. T cells respond only to antigens that sits on other cells, not to such elements that are freely floating in the bloodstream.

But it was clear that T cells needed something more than the antigen to be able to react. This “something” was a hereditary factor that varied from person to person, and which was called HLA (human leukocyte antigen). How this worked was unclear. The model that seemed the most likely was that T cells saw antigens that were nestling close to HLA on cell surfaces.

In 1987 the long awaited answer finally came. A young researcher, Pamela Bjorkman, had succeeded in taking a picture of an HLA molecule with an antigen. Amazingly, she told about her results for the first time at an immunology conference in Oslo.


Various depictions of the HLA groove. Pamela’s groove is a schematic drawing of the protein structure of HLA, as seen from above by the T cells

Pamela showed that the HLA molecule forms an elongated groove, where a fragment of the foreign substance, a peptide, fits in perfectly. Those who were present and heard her story, still remembers the feeling: “Yes! So be it”. Everyone immediately realized that this was a huge breakthrough, much like when Watson and Crick 20 years earlier showed the DNA molecule for the first time.

The following year I started my research. I was to use Pamela’s image of the groove to understand how HLA molecules predispose to disease. So did thousands of researchers worldwide. Others set about designing cancer vaccines that could fit into the HLA groove. Still others examined how the HLA groove bound peptides, and whether it was possible to replace one peptide with another. Did the peptides outright compete for space in the groove?

The fact that my boyfriend pr love letters had absorbed so much about the HLA molecules’ form and function, to the extent that a poor French spring bed reminded him in his sleep of the HLA groove, illustrates well the huge impact Pamela’s image of the groove had on immunologists at the time.

The discovery of the groove has been so crucial for our understanding of the immune system, that many of the posts on this blog are going to touch upon the groove in one way or another.

When Pamela had finished her presentation in Oslo in May 1987, it so happened that a journalist from the Norwegian Broadcasting Company (NRK) called one of the organizers: “Were there any interesting News from the Conference?”.

Sigbjørn Fossum, still in euphoria over Pamela’s results, told him excitedly about the immense breakthrough he had just witnessed. “Does this mean that you will soon find a treatment for diabetes”, asked the journalist. Fossum admitted that it would probably still take some time.

The journalist immediately lost interest, and asked if there were any news about HIV. Resignedly, Fossum mentioned that a Norwegian scientist had reported that HIV could penetrate the skin cells he cultivated in the laboratory. The NRK report from the Immunology meeting in Oslo read: “HIV is spread through skin!”

Blogpost by Anne Spurkland, 09/22/12
Translated from Norwegian 12th March 2016

4 thoughts on “The groove

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