CD1

CD1 (cluster of differentiation 1) is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. CD1 glycoproteins are structurally related to the class I MHC molecules, however, in contrast to MHC class 1 proteins, they present lipids, glycolipids and small molecules antigens, from both endogenous and pathogenic proteins, to T cells and activate an immune response.

T cells recognise CD1 using TCR αβ, γδ, or CD36 family members. T cells that are activated by CD1-antigen complexes are called CD1-restricted T cells. 10% of all αβ T lymphocytes in human peripheral blood are Cd1-restricted, out of which, the most abundant are the T cells specific for CD1c. The first antigen that was discovered to be able to bind CD1 and then be recognised by TCR is C80 mycolic acid. Even though their precise function is unknown, The CD1 system of lipid antigen recognition by TCR offers the prospect of discovering new approaches to therapy and developing immunomodulatory agents.

CD1a, CD1b and CD1c (group 1 CD1 molecules) are expressed on cells specialized for antigen presentation.
CD1e is also considered a group 1 CD1 molecule, even though it does not function in antigen presentation, contrasting the other isoforms.
CD1d (group 2 CD1) is expressed in a wider variety of cells.

CD1e is an intermediate form, a soluble lipid transfer protein that is expressed intracellularly. It does not present lipid antigens to T cells, rather plays a role in the processing of lipid antigens and loading them onto other CD1 molecules.

Structure

CD1 proteins consist of a heavy chain with α1, α2, and α3 domains and a transmembrane domain which anchors it to the cell membrane. Much like the MHC molecules, the CD1 heavy chain associates with β2-microglobulin and its binding groove consists of two antiparallel α-helices, placed atop a β-sheet platform. The antigen-binding cleft architecture of CD1 proteins consists of A', C', F' and T' binding pockets and C' and D'/E' accessory portals, which act to accommodate the aliphatic hydrocarbon chains present in lipid, glycolipid, phospholipid, or lipopeptide antigens. CD1 antigen binding clefts are defined by locations of named portals where antigens protrude. Specifically, they express four orthologs of the group 1 CD1b protein and three orthologs of CD1c, as well as one ortholog of CD1d.

Ruminants

Cows have one copy each of CD1a and CD1e, several copies of CD1b, and no copies of CD1c. Ruminants including cows were previously thought to have no functional copies of CD1d (only pseudogenes) due to lack of reaction to αGalCer when tested using mouse iNKT cells, but later research has shown CD1d to be expressed and the genes for the NKT machinery to be present. It turns out bovine CD1d has an altered binding pocket causing a different binding "pose". The change also incurs a limit on the length of the glycosphingolipid antigen.

Because 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. M. bovis is also very similar to M. tuberculosis genetically. Cows are a valuable model organism for studying immune responses to tuberculosis with many similarities to humans. Nevertheless, they have their own special features such as the aforementioned CD1 repertoire and a special division of labor among δγ T cells by expression of WC1, a protein not found in primates.

Structure

Ruminants

References

External links