Howard Hughes Medical Institute (HHMI) researchers have isolated a protein receptor in chickens that is responsible for transferring
antibodies from mother to offspring - a function critical to bestowing a temporary immunity that protects the young against infection until their own immune systems begin functioning.
The receptor molecule is a functional counterpart to one found in mammals, including humans, that also attaches to antibodies and transfers them to offspring. In the case of humans, the antibodies pass through the placenta before birth. In chickens, they are passed to embryos across the yolk sac membrane of the egg.
The researchers were surprised to find, however, that although the mammalian and chicken receptors play the same basic role, their structures were unique, revealing different evolutionary routes to the same function. According to the researchers, the discovery raises intriguing questions about how the chicken receptor functions and its relationship to similar proteins in mammals.
Led by HHMI investigator Pamela J. Bjorkman at the California Institute of Technology, the researchers published their findings in the May 2004 issue of the journal Immunity.
In their studies, the researchers sought to isolate the avian counterpart of the receptor called FcRn (the neonatal Fc receptor), which in mammals transfers the antibody immunoglobulin G (IgG) from mother to offspring. FcRn bears an intriguing structural resemblance to molecules called major histocompatibility complex (MHC) proteins, which function in the vertebrate adaptive immune response by presenting antigenic peptides to T cells. Previous studies had indicated that the avian antibody immunoglobulin Y (IgY) was transferred from hens to chicks by a receptor, but its relationship to MHC molecules had not been investigated.
“In the sense that this receptor was moving IgY, which is the counterpart of IgG in mammals, it sounded like it was the avian equivalent of FcRn,” said Bjorkman. “But all that had been shown previously was that there was an IgY binding activity on yolk sacs. Nobody had purified or characterized the protein.”
To isolate the avian receptor, the researchers exploited the fact that, as is also the case for IgG binding to FcRn, the IgY antibody tends to attach to its receptor under slightly acidic conditions, and to release from the receptor under slightly basic conditions. The researchers knew they could carry out a relatively straightforward isolation of the FcRY receptor by passing a solution of yolk sacs through a separation column containing IgY under acid conditions — causing the receptor to stick to the IgY. Then they could use a flow of more basic liquid to flush out only the IgY-binding protein.
“When we did that, it was absolutely pure and clean,” said Bjorkman. “There was nothing else there.” Thus, she said, they knew immediately that they had likely identified the receptor responsible for IgY transport to chicks. Further studies of the protein showed that it had the appropriate binding properties to IgY.