CD1 glycoproteins can be classified primarily into two groups which differ in their lipid anchoring.[2]
CD1a, CD1b and CD1c (group 1 CD1 molecules) are expressed on cells specialized for antigen presentation.[3]
CD1d (group 2 CD1) is expressed in a wider variety of cells.
CD1e is an intermediate form, expressed intracellularly, the role of which is currently unclear.[4]
In humans
Group 1
Group 1 CD1 molecules have been shown to present foreign lipid antigens, and specifically a number of mycobacterial cell wall components, to CD1-specific T cells.
Group 2
The natural antigens of group 2 CD1 are not well-characterized, but a synthetic glycolipid, alpha-galactosylceramide, originally isolated from a compound found in a marine sponge, has strong biologic activity.
Group 2 CD1 molecules activate a group of T cells, known as Natural killer T cells because of their expression of NK surface markers such as CD161. Natural Killer T (NKT) cells are activated by CD1d-presented antigens, and rapidly produce Th1 and Th2 cytokines, typically represented by interferon-gamma and IL-4 production.
The group 2 (CD1d) ligand alpha-galactosylceramide is currently in phase I clinical trials for the treatment of advanced non-hematologic cancers.
In cows and mice
Mice lack the group 1 CD1 molecules, and instead have 2 copies of CD1d. Thus, mice have been used extensively to characterize the role of CD1d and CD1d-dependent NKT cells in a variety of disease models.
It has recently been shown that cows lack the group 2 CD1 molecules, and have an expanded set of group 1 CD1 molecules.[5] Because of this and the fact that cows are a natural host of Mycobacterium bovis, a pathogen in humans as well, it is hoped that studying cows will yield insights into the group 1 CD1 antigen-presenting system.
References
^ Porcelli S, Brenner MB, Greenstein JL, Balk SP, Terhorst C, Bleicher PA (1989). "Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes". Nature341 (6241): 447–50. doi:10.1038/341447a0. PMID 2477705.
^ Zajonc DM, Wilson IA (2007). "Architecture of CD1 proteins". Curr. Top. Microbiol. Immunol.314: 27–50. PMID 17593656.
^ Sköld M, Behar SM (2005). "The role of group 1 and group 2 CD1-restricted T cells in microbial immunity". Microbes Infect.7 (3): 544–51. doi:10.1016/j.micinf.2004.12.012. PMID 15777730.
^ Angenieux C, Salamero J, Fricker D, Cazenave JP, Goud B, Hanau D, de La Salle H (2000). "Characterization of CD1e, a third type of CD1 molecule expressed in dendritic cells". J. Biol. Chem.275 (48): 37757–64. doi:10.1074/jbc.M007082200. PMID 10948205.
^ Van Rhijn I, Koets AP, Im JS, Piebes D, Reddington F, Besra GS, Porcelli SA, van Eden W, Rutten VP (2006). "The bovine CD1 family contains group 1 CD1 proteins, but no functional CD1d". J. Immunol.176 (8): 4888–93. PMID 16585584.