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The two-locus model of H2


Working on H2 with Hugh McDevitt
Jan Klein Scientist
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So what has happened that changed the situation? I have to now go back to Stanford to make the point. So when I got there, as I said, I realized that Len Herzenberg is not interested in H2 at all. But there was fortunately somebody with whom I could talk about H2 to my heart's content and that was Hugh McDevitt. He arrived recently to Stanford with a very interesting discovery. He realized that if he immunises mice with artificial antigen... antigen that was a protein consisting of only four types of amino acids, that was called TGAL for the abbreviations of the amino acids, that some mice made antibodies very high titre... very high level of antibodies, others very low. And he did crosses and he realized that what decides whether it's high or low is controlled by a single gene. There was one gene that decided this strain will make... that has the gene... will make high level of antibodies and another gene... an allele that would practically make no antibodies against the antigen.

So that was very interesting, but even more interesting was already the result that he was getting while I was still there. He already knew... he had already indications of this. It was not published yet, but he had indications of this. Or it might have been published at the end of my stay. I don't really remember. But that he... where the gene maps, and by now you would guess where it was. It mapped to the H2. It was very tightly associated with the H2. This was very interesting. So our question was, okay where? What... does it have any relationship to H2 or is it there by chance this linkage or something? The fact was both were somehow involved in immune response. So maybe there is a relationship or not. So in the meantime we were... the H2 Club... and we were making the system more and more complex. But we were also mapping the system... we were using the recombinants that I mentioned before to find out where this... can we divide this system into units? Well, we could. In the end there were about eight different segments that we thought we mapped in a particular order from the K to the D. Those were the extremes and in between were the Shreffler's protein, which mapped actually inside of the H2. And before I forget to mention it, it turned out to be a complement component four. So the mysterious protein for a long time turned out to be identical with something that was known already to exist. But there were all those regions.

So you know to relate now the gene that Hugh McDevitt discovered to these regions and map it all became the priority that we were... Hugh primarily was involved in. Incidentally he called the gene Immune Response Gene 1. So IR1, so it was an IR1 locus. So since... and we talked and I told him we had some recombinants and he got some recombinants from Stimpfling and Snell and Shreffler. And so he was involved now in mapping the IR1 in relationship to all these regions in the H2.

Born in 1936, Jan Klein is a Czech-American immunologist who co-founded the modern science of immunogenetics – key to understanding illness and disease. He is the author or co-author of over 560 scientific publications and of seven books including 'Where Do We Come From?' which examines the molecular evolution of humans. He graduated from the Charles University at Prague in 1955, and received his MS in Botany from the same school in 1958. From 1977 to his retirement in 2004, he was the Director of the Max Planck Institute for Biology at Tübingen, Germany.

Listeners: Colm O'hUigin

Colm O'hUigin is a senior staff scientist at the US National Cancer Institute. He received his BA, MSc and PhD at the Genetics Department of Trinity College, Dublin where he later returned as a lecturer. He has held appointments at the Center for Population and Demographic Genetics, UT Houston, and at the University of Cambridge. As an EMBO fellow, he moved in 1990 to the Max Planck Institute for Biology in Tübingen, Germany to work with Jan Klein and lead a research group studying the evolutionary origins of immune molecules, of teeth, trypanosomes and of species.

Tags: TGAL, H2, Immune Response Gene 1, IR1, recombinants, H2 Club, Hugh O'Neill McDevitt, George Davis Snell, Jack H Stimpfling, Donald C Shreffler, Leonard Arthur Herzenberg

Duration: 4 minutes, 50 seconds

Date story recorded: August 2005

Date story went live: 24 January 2008