on August 20th, 2015 No Comments
When Hugo Hilton began working at Stanford as a young researcher several years ago, his supervisor set him to work on a minor problem so he could practice some standard lab techniques. His results, however, were anything but standard. His supervisor — senior research scientist Paul Norman — told him to do the work over, convinced the new guy had made a mistake. But Hilton, got the same result the second time, so Norman made him do it over again. And then again.
“This was Hugo’s first PCR reaction in our lab and I gave him the DNA,” recalled Norman, “and the very first one he did, he pulled out this mutation. I was convinced that he’d made a mistake.” Norman even quietly redid the work himself. But the gene variant was real.
Norman and colleagues had been studying the same group of immune genes for decades and he knew them like the back of his hand. Yet he was astonished by what Hilton had stumbled on — a mutation that switched a molecular receptor from one protein target to another. It would be as if you bent your house key ever so slightly and discovered it now opened the door to your neighbor’s apartment — but not yours.
And the mutation, far from causing some illness, might contribute to healthier mothers and babies. Parallel research at another institution suggests the odd gene most likely changes the placenta during early pregnancy, leading to better-nourished babies and a reduced risk of pre-eclampsia, a major cause of maternal death.
The surprising finding grew out of a long-term effort to understand how immune system genes make us reject organ transplants. A big part of that puzzle is understanding how much immune genes can vary. On the surfaces of ordinary cells are proteins called HLAs. Combinations of these proteins mark cells in a way that makes each person’s cells so nearly unique that the immune system can recognize cells as either self or not self. When a surgeon transplants a kidney, the recipient’s immune system can tell that the kidney is someone else’s — just from its cell surface HLA proteins. The patient’s immune system then signals its natural killer cells to attack the transplanted kidney. The key to all that specificity is the huge variation in the genes for the HLA proteins.