STRUCTURE

CD1a is a non-polymorphic type 1 integral glycoprotein with a similar structure to MHC class I molecules. CD1a is composed of a short cytoplasmic tail, a transmembrane domain and an extracellular part that contains 3 α domains.^1-2 The α1 and α2 domains bind to the ligand.² The α3 domain interacts with β-2 microglobulin forming a heterodimer. 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 (Warsz). 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

CD1a ligands are sulfatide¹, didehydroxymycobactins², phosphatidylcholine and phosphatidylethanolamine³, urushiol⁴, squalene⁵, triacylglyceride⁵, wax esters⁵, and the TCR.⁶ It associates with β-2 microglobulin, MHC class II, invariant chain and CD9 in cis.^7-8

Intracellular associate molecules

No intracellular associate molecules have been reported.

1. Zajonc DM, Elsliger MA, Teyton L, Wilson IA. Crystal structure of CD1a in complex with a sulfatide self antigen at a resolution of 2.15 A. Nat Immunol. 2003;4:808-15.
2. Moody DB, Young DC, Cheng TY, Rosat JP, Roura-Mir C, O'Connor PB, Zajonc DM, Walz A, Miller MJ, Levery SB, Wilson IA, Costello CE, Brenner MB. T cell activation by lipopeptide antigens. Science. 2004;303:527-31.
3. Agea E, Russano A, Bistoni O, Mannucci R, Nicoletti I, Corazzi L, Postle AD, De Libero G, Porcelli SA, Spinozzi F. Human CD1-restricted T cell recognition of  lipids from pollens. J Exp Med. 2005;202:295-308.
4. Kim JH, Hu Y, Yongqing T, Kim J, Hughes VA, Le Nours J, Marquez EA, Purcell AW, Wan Q, Sugita M, Rossjohn J, Winau F. CD1a on Langerhans cells controls inflammatory skin disease. Nat Immunol. 2016;17:1159-66.
5. De Jong A, Cheng TY, Huang S, Gras S, Birkinshaw RW, Kasmar AG, Van Rhijn I, Peña-Cruz V, Ruan DT, Altman JD, Rossjohn J, Moody DB. CD1a-autoreactive T cells  recognize natural skin oils that function as headless antigens. Nat Immunol. 2014;15:177-85.
6. Birkinshaw RW, Pellicci DG, Cheng TY, Keller AN, Sandoval-Romero M, Gras S, de Jong A, Uldrich AP, Moody DB, Godfrey DI, Rossjohn J. αβ T cell antigen receptor  recognition of CD1a presenting self lipid ligands. Nat Immunol. 2015;16:258-66.
7. Zajonc DM. The CD1 family: serving lipid antigens to T cells since the Mesozoic era. Immunogenetics. 2016;68:561-76.
8. Sloma I, Zilber MT, Vasselon T, Setterblad N, Cavallari M, Mori L, De Libero G, Charron D, Mooney N, Gelin C. Regulation of CD1a surface expression and antigen presentation by invariant chain and lipid rafts. J Immunol. 2008;180:980-7.

CD1a is highly expressed on Langerhans cells.¹ CD1a is also expressed on dendritic cells and on thymocytes, with higher intensity in double-positive and with lesser in single-positive.

1. Kaczmarek R, Pasciak M, Szymczak-Kulus K, Czerwinski M. CD1: A Singed Cat of the Three Antigen Presentation Systems. Arch Immunol Ther Exp (Warsz). 2017;65:201-214.
2. Coventry B, Heinzel S. CD1a in human cancers: a new role for an old molecule.  Trends Immunol. 2004;25:242-8.

CD1a, as other members of the CD1 family, is involved in the immune response by presenting self and non-self lipid and glycolipid antigens to T cells.¹ Interestingly, CD1a participates in bee and wasp venom allergy and in antitumor immune responses.^2-3

1. Coventry B, Heinzel S. CD1a in human cancers: a new role for an old molecule.  Trends Immunol. 2004;25:242-8.
2. Subramaniam S, Aslam A, Misbah SA, Salio M, Cerundolo V, Moody DB, Ogg G. Elevated and cross-responsive CD1a-reactive T cells in bee and wasp venom allergic individuals. Eur J Immunol. 2016;46:242-52.
3. La Rocca G, Anzalone R, Bucchieri F, Farina F, Cappello F, Zummo G. CD1a and antitumour immune response. Immunol Lett. 2004;95:1-4.

Cell marker

Used for diagnosis and characterization of T-cell precursor acute lymphoblastic leukemia/lymphoma¹. It is also useful as a marker of Langerhans cells and dendritic cells.² Furthermore, the number of CD1a-positive dendritic cells is associated with a better prognosis in ovarian cancer, papillary thyroid carcinoma, squamous cell carcinoma of the tongue and oral squamous cell carcinoma.^3-6

1. van Dongen JJ, Lhermitte L, Böttcher S, Almeida J, van der Velden VH, Flores-Montero J, Rawstron A, Asnafi V, Lécrevisse Q, Lucio P, Mejstrikova E, Szczepański T, Kalina T, de Tute R, Brüggemann M, Sedek L, Cullen M, Langerak AW, Mendonça A, Macintyre E, Martin-Ayuso M, Hrusak O, Vidriales MB, Orfao A; EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708). EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive  and malignant leukocytes. Leukemia.;26:1908-75.
2. Coventry B, Heinzel S. CD1a in human cancers: a new role for an old molecule. Trends Immunol. 2004;25:242-8.
3. Eisenthal A, Polyvkin N, Bramante-Schreiber L, Misonznik F, Hassner A, Lifschitz-Mercer B. Expression of dendritic cells in ovarian tumors correlates with clinical outcome in patients with ovarian cancer. Hum Pathol. 2001;32:803-7.
4. Goldman SA, Baker E, Weyant RJ, Clarke MR, Myers JN, Lotze MT. Peritumoral CD1a-positive dendritic cells are associated with improved survival in patients with tongue carcinoma. Arch Otolaryngol Head Neck Surg. 1998;124: 641-6.
5.  Hilly O, Rath-Wolfson L, Koren R, Mizrachi A, Hamzany Y, Bachar G, Shpitzer T. CD1a-positive dendritic cell density predicts disease-free survival in papillary  thyroid carcinoma. Pathol Res Pract. 2015;211:652-6.
6. Jardim JF, Gondak R, Galvis MM, Pinto CAL, Kowalski LP. A decreased peritumoral CD1a+ cell number predicts a worse prognosis in oral squamous  cell carcinoma. Histopathology. 2017 Oct 11.

Therapeutic

To our knowledge, no therapy targeting CD1a has been approved. However, a preliminary study of anti-CD1a antibodies has shown to decrease inflammation in inflammatory skin disease.¹

1. Kim JH, Hu Y, Yongqing T, Kim J, Hughes VA, Le Nours J, Marquez EA, Purcell AW, Wan Q, Sugita M, Rossjohn J, Winau F. CD1a on Langerhans cells controls inflammatory skin disease. Nat Immunol. 2016 Oct;17(10):1159-66. doi: 10.1038/ni.3523. Epub 2016 Aug 22.