Moms and pups sniff out immune genes.

Given how similar newborns can look, forgive parents if they have trouble picking out their bundle of joy from the swaddled masses in a maternity ward. Perhaps they should sniff each one. After all, among animals, many parents and offspring recognize each other by scent.

The major histocompatibility complex (MHC), a cluster of genes important to the immune system, is at the heart of this olfactory ability, suggests a mouse study in the Sept. 12 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.

"This is the first indication of a set of genes that is responsible for providing the individual signature that both the mother and offspring recognize," says coauthor Gary K. Beauchamp of the Monell Chemical Senses Center in Philadelphia.

The MHC genes encode cell-surface proteins that display bits of invading bacteria, viruses, and other microbes, thereby helping the immune system recognize harmful germs. The MHC of a mouse or a person contains dozens of genes, some having more than 100 versions. MHC variation creates a problem for people needing an organ transplant; their bodies may reject donor tissue if its MHC profile is too dissimilar.

In the 1970s, the diversity of the MHC prompted the late biologist Lewis Thomas to speculate that this set of genes confers identifying odors upon people. He even suggested that for a person needing a transplant, dogs could sniff out a donor having similar MHC genes. As Thomas predicted, many studies have now shown that the MHC influences odortype, the signature scent of a person or animal.

In recent years, studies on the role of the MHC in mating have backed the maxim that opposites attract. Animals, and even people, seem to prefer mates with dissimilar MHC genes. In one study, women favored the smell of sweaty T-shirts from men with MHC genes unlike their own. Such a preference may promote MHC diversity, creating offspring with strong immune systems.

Beauchamp and his colleagues, who conducted some of the mating studies on mice, have now extended their MHC work to mother-pup recognition. They considered two strains of mice whose only genetic differences are in the MHC.

First, the scientists observed female mice retrieving pups born to other females of both strains. In general, a foster mother first went after pups with her own MHC complement. This suggests that female mice use MHC-influenced odortypes to recognize their young, says Beauchamp.

The scientists also tested pups by placing them in a Y-shaped maze. One arm held soiled cedar shavings from cages of mice with the same MHC genes as the pups, while the other had shavings from the cages of the other strain.

The pups preferred to spend time in one arm over the other and based their choice on the foster mothers raising them. If reared by a female mouse with dissimilar MHC genes, says Beauchamp, pups chose the arm bearing the scent of the female's strain over the one smelling of the pups' own strain.

"This is the first study that has moved the MHC out of the mating realm," notes Peter Hepper of the Queen's University of Belfast in Northern Ireland.

While the study reveals that mice use MHC-influenced odors to identify each other, it suggests that experience governs whom the pups want to be around. "In my mind, there's no MHC preference. It's a learned thing," says Hepper.

Beauchamp suggests that human parents and their babies also establish a crucial bond via smell. A 1998 study, he notes, found that parents could pick out the amniotic fluid that had bathed their infant simply by odor. Some scientists are even exploring whether a mother's smell soothes an infant.

Beauchamp and his colleagues continue to investigate how the MHC generates an odortype. They contend that the proteins encoded by the genes bind to and transport molecules responsible for the body's scent (SN: 3/13/99, p. 174).

"It's quite clear that the MHC produces individually distinct odors. The way that it does that has yet to be fully understood," says Hepper.