Bird genes give new insights into the origins of lipid antigen presentation

Abstract

Which came first: the chicken or the egg? This famous question has given the chicken much prominence as a metaphor for difficult questions about evolution. Now it seems that chickens have landed again in the middle of an interesting evolutionary question by becoming the first nonmammalian species shown to possess genes for CD1, a family of immunologically important molecules known to be present in most, if not all, mammals. Mammalian CD1 proteins are believed to perform a significant role in adaptive immunity by functioning as antigen-presenting molecules for T cell responses to a unique class of self and foreign antigens (1). However, CD1 has diverged considerably from other known antigen-presenting molecules, which are encoded by the class I and II genes of the major histocompatibility complex (MHC), raising intriguing questions about the evolutionary relationship of these molecules. In this issue of PNAS, two groups report the identification of CD1 genes in the domestic chicken ( Gallus domesticus ) and its immediate wild ancestor, the Red Jungle Fowl ( Gallus gallus ), thus providing the first examples of CD1 genes in a non-mammalian species (2, 3). By extending the origin of CD1 back at least 300 million years to the time of the last common ancestor of birds and mammals, these findings support the view of CD1 as an ancient lineage of antigen-presenting molecules that, like the MHC class I and II families, was part of the early foundations of the adaptive immune system. The CD1 system was first brought to light by cloning of the five human CD1 genes by Calabi and Milstein (4), whose pioneering studies identified clear homology and structural similarity of CD1 molecules to MHC class I and II. However, the relatively low levels of sequence homology between CD1 and the MHC-encoded molecules suggested a very distant evolutionary relationship and …