CD1

CD1 (cluster of differentiation 1) is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells.

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Types

CD1 glycoproteins can be classified primarily into two groups which differ in their lipid anchoring.^[1]

CD1a, CD1b and CD1c (group 1 CD1 molecules) are expressed on cells specialized for antigen presentation.^[2]

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.^[3]

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.^[4] 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

1. ^ Zajonc DM, Wilson IA (2007). "Architecture of CD1 proteins". Curr. Top. Microbiol. Immunol. 314: 27-50. PMID 17593656.
2. ^ 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.
3. ^ Angenieux C, Salamero J, Fricker D, et al (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.
4. ^ Van Rhijn I, Koets AP, Im JS, et al (2006). "The bovine CD1 family contains group 1 CD1 proteins, but no functional CD1d". J. Immunol. 176 (8): 4888-93. PMID 16585584.