A question about the biology of a simple marine organism sparks an advance in AIDS research.

AIDS is a disease of the human immune system, but the story of how sea squirts won a role in AIDS research begins not with immunity but with fertilization. Like us, Botryllus, and other sea squirts begin life as a single fertilized egg. After fertilization, this egg cleaves, maker more and more cells, and ultimately develops into a larva that looks somewhat like a frog tadpole. These animals have a peculiar property that sets them apart from us or any other true vertebrate: each individual animal is hermaphroditic, producing both sperm and eggs.

Theoretically, these animals should be able to self-fertilize' but this rarely happens. Sea squirts employ the same principles to prevent self-fertilization between close relatives as they employ in their control of transplantation. Thus, just as the blood cells of two related Botryllus colonies will not bind to and kill each other, the sperm from an animal cannot bind to and fertilize it's own eggs.

This suggested to a startling possibility; not only might the principles of transplantation and fertilization in these creatures be similar, but the transplantation markers involved in the process might be similar as well. To test that possibly, the direct experiment seemed best: mix sea squirt sperm cells with blood cells. Would the sperm bind to the blood cells? Would they distinguish between blood cells from the same animal (self) and a different animal(non-self)?
The answer is yes. Just as in the case with sperm and eggs, if you take blood and sperm from animal A and mix them together, the sperm will not bind to self blood cells. The same is true for animal B. But if you mix sperm from animal A with blood cells from animal B - or sperm from B with blood from animal A - the sperm will bind to and penetrate the other animal's blood cells. Using the electron microscope, we can see their heads inside the cells. We were very surprised at how clear the result was.

Out of curiosity, they decided to conduct the same experiment with human sperm and blood cells. No one had ever done an experiment of the kind with this objective in mind. When we mixed blood cells from a normal donor with sperm from a normal donor, the sperm bound to and penetrated the blood cells.

As in sea squirts, it turn out the receptor for sperm - the substance on the blood cells to which the sperm sticks - is a self-recognition molecule. In the human studies, we know a little more about it's identity; it is a structure called HLA-DR. HLA-DR is a blood cell specific transplantation molecule found on many white blood cells. It is important in many diseases, including AIDS.