Genetics of CD1 Molecules

Abstract

Cluster of differentiation 1 (CD1) molecules are a family of MHC class I-like glycoproteinsl. Interestingly, the first monoclonal antibody that recognized an MHC class I (or class I-like) molecule on human thymocytes was against CD1^{2, 3}hence its #1 designation. The genes encoding these molecules are present on chromosome 1 in humans and 3 in the mouse^4-6; this is in contrast to human chromosome 6 and murine chromosome 17, on which the respective MHC gene loci resider. The genes encoding the human CD1 molecules were discovered by Milstein in 1986^{4, 7}. These were found in an analysis of human genomic DNA and discovered to be a family of genes encoding MHC class I-like molecules. Like that seen in the MHC class I molecules as described above by Drs. Candon and Margulies, CD1 molecules also consist of a heavy chain comprised of a1, a2, and a3 domains, and are noncovalently associated with 13₂microglobulin⁸. A cluster of fivecdlgenes were identified and designatedcdla, cdlb, cdlc, cdldandcdle.These five genes are physically very close to one another and likely arose by gene duplication, as the percent homology amongst the variouscdlgenes is approximately 80% in the a3 domain, for example. In spite of this, thecdlgenes are sufficiently different to be separated into two groups. Group Icdlgenes (and their gene products) consist ofcdla, cd1 bandcdlc.The gene encoding CD 1 d molecules is the sole member of Group II. In contrast, thecdlegene is considered to be “intermediate”¹. It should be noted, however, that although there is some divergence of thecdlgenes (as would be expected over time), the fivecdlgenes are most homologous in the a3 domain—the portion of the CD1 heavy chain to which the ß₂microglobulin light chain binds. An interesting feature of the