STRUCTURE

CD1c is a non-polimorphic type 1 integral glycoprotein with a similar structure to MHC class I molecules. CD1c is composed of a short cytoplasmic tail, a transmembrane domain and an extracellular region that contains 3 α domains.^1-2 The α1 and α2 bind to the ligand.² The α3 domain interacts with β-2 microglobulin, forming a heterodimer. ² The cytoplasmic tail contains a tyrosine-based motif for adaptors binding. ²

1. Kaczmarek R, Pasciak M, Szymczak-Kulus K, Czerwinski M. CD1: A Singed Cat of the Three Antigen Presentation Systems. Arch Immunol Ther Exp. 2017;65:201-214.

2. Zajonc DM. The CD1 family: serving lipid antigens to T cells since the Mesozoic era. Immunogenetics. 2016;68:561-76.

LIGANDS

Extracellular

CD1c ligands include isoprenoid glycolipids¹, phosphatidylcholines², glycerophospholipids², sphingomyelin², sulfatide³, phosphomycoketide lipids^4-5, N-terminally acylated lipopeptides and the TCR. ^6-7 It interacts with β-2 microglobulin in cis.⁸

Intracellular associate molecules

CD1c can be associated with AP-3.⁹

1. Moody DB, Ulrichs T, Mühlecker W, Young DC, Gurcha SS, Grant E, Rosat JP, Brenner MB, Costello CE, Besra GS, Porcelli SA. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000;404:884-8.

2. Haig NA, Guan Z, Li D, McMichael A, Raetz CR, Xu XN. Identification of self-lipids presented by CD1c and CD1d proteins. J Biol Chem. 2011;286:37692-701.

3. Shamshiev A, Gober HJ, Donda A, Mazorra Z, Mori L, De Libero G. Presentation of the same glycolipid by different CD1 molecules. J Exp Med. 2002;195:1013-21.

4. Scharf L, Li NS, Hawk AJ, Garzón D, Zhang T, Fox LM, Kazen AR, Shah S, Haddadian EJ, Gumperz JE, Saghatelian A, Faraldo-Gómez JD, Meredith SC, Piccirilli JA, Adams EJ. The 2.5 Å structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation. Immunity. 2010;33:853-62.

5. Ly D, Kasmar AG, Cheng TY, de Jong A, Huang S, Roy S, Bhatt A, van Summeren RP, Altman JD, Jacobs WR Jr, Adams EJ, Minnaard AJ, Porcelli SA, Moody DB. CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. J Exp Med. 2013;210:729-41.

6. Van Rhijn I, Young DC, De Jong A, Vazquez J, Cheng TY, Talekar R, Barral DC, León L, Brenner MB, Katz JT, Riese R, Ruprecht RM, O'Connor PB, Costello CE, Porcelli SA, Briken V, Moody DB. CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids. J Exp Med. 2009;206:1409-22.

7. Roy S, Ly D, Li NS, Altman JD, Piccirilli JA, Moody DB, Adams EJ. Molecular basis of mycobacterial lipid antigen presentation by CD1c and its recognition by αβ T cells. Proc Natl Acad Sci U S A. 2014;111:E4648-57.

8. Zajonc DM. The CD1 family: serving lipid antigens to T cells since the Mesozoic era. Immunogenetics. 2016;68:561-76.

9. Van Rhijn I, Ly D, Moody DB. CD1a, CD1b, and CD1c in immunity against mycobacteria. Adv Exp Med Biol. 2013;783:181-97.

CD1c is expressed on thymocytes, monocytes and dendritic cells, including epidermal Langerhans cells, interdigitating and dermal dendritic cells. ^1-3 In addition, CD1c is also present in germinal center, mantle zone and splenic marginal zone B cells, but also in a subset of circulating B cells.^1,4

1. Dougan SK, Kaser A, Blumberg RS. CD1 expression on antigen-presenting cells. Curr Top Microbiol Immunol. 2007;314:113-41.

2. Reinink P, Van Rhijn I. Mammalian CD1 and MR1 genes. Immunogenetics. 2016;68:515-23.

3. Schrøder M, Melum GR, Landsverk OJ, Bujko A, Yaqub S, Gran E, Aamodt H, Bækkevold ES, Jahnsen FL, Richter L. CD1c-Expression by Monocytes - implications for the Use of Commercial CD1c+ Dendritic Cell Isolation Kits. PLoS One. 2016;11:e0157387.

4. Adams EJ. Diverse antigen presentation by the Group 1 CD1 molecule, CD1c. Mol Immunol. 2013;55:182-5.

CD1c, as other members of the CD1 family, is involved in the immune response by presenting self and non-self lipids and glycolipid antigens to T cells TCR-αβ and T cells TCR-γδ. For instance, CD1c presents lipids from bacteria such as Mycobacterium tuberculosis and M. avium. ¹

1. Adams EJ. Diverse antigen presentation by the Group 1 CD1 molecule, CD1c. Mol Immunol. 2013;55:182-5.

Cell marker

CD1c can be used as a marker of CD14- dendritic cells, CD14+ monocytes and splenic marginal zone B cells.^1-3

1. Collin M, McGovern N, Haniffa M. Human dendritic cell subsets. Immunology. 2013;140:22-30.

2. Schrøder M, Melum GR, Landsverk OJ, Bujko A, Yaqub S, Gran E, Aamodt H, Bækkevold ES, Jahnsen FL, Richter L. CD1c-Expression by Monocytes - Implications for the Use of Commercial CD1c+ Dendritic Cell Isolation Kits. PLoS One. 2016;11:e0157387.

3. Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, Plebani A, Kumararatne DS, Bonnet D, Tournilhac O, Tchernia G, Steiniger B, Staudt LM, Casanova JL, Reynaud CA, Weill JC. Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood. 2004;104:3647-54.

Therapeutic

To our knowledge, no therapy targeting CD1c has been approved.