• CD1A [HUGO gene name]
• R4

MAJOR LINKS FOR CD1a  

• NCBI LocusLink Record: 909
• Mendelian Inheritance in Man (OMIM): 188370
• SwissProt annotated protein record: P06126

CELLULAR FUNCTION OF CD1 Family  

• CD1s have been demonstrated to restrict T-cell responses to non-peptide lipid and glycolipid antigens [reviewed in reference 4].
• CD1 molecules could be involved in the delivery of signals for lymphocyte activation. Some anti-CD1 mAbs produced inhibition of bacterial superantigen thymocytes proliferation. On PBMC, depending on the epitope recognized by the mAb, we observed an inhibitory or enhanced effect on the proliferative response to the phosphokinase C (PKC) activator phorbol myristate acetate (PMA) [M. Salomone, unpublished observations]
• The expression of CD1 molecules on thymocytes has been related to a role in thymic T-cell development. NK1+ cells a subset of T cells found in high frequencies in the mature compartment of the mice thymus are involved in the development of NK cells.[10]. These cells, found in high frequencies in bone marrow and liver, have CD1 molecules as their ligand. It has been postulated that through their NK-like activity, the liver is actively involved in the peripheral cell deletion of T cells arriving from the intestine through the portal vein. By this mechanism, these cells may be involved in the induction of oral tolerance [3]

DISEASE RELEVANCE OF CD1 Family AND FUNCTION OF CD1 Family IN INTACT ANIMAL   - No information

• Families in which CD1a is a member
  • CD1a-->CD1-->MHC I-like-->MHC family-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD1 Family  

• Glycosylated type I transmembrane polypeptide alpha chain non-covalently associated with beta 2 microglobulin
• CD1 genes consist of multiple exons, with functional domains of the polypeptide encoded by separate exons (5' UT- leader, a1, a2, a 3, transmembrane, and cytoplasmic-3')
• a1, a2 and a3 domains encode non-polymorphic extracellular domains about 90 amino acids long [5]
• On the basis of sequence homology, CD1 molecules can be classified into group 1 which includes CD1a, CD1b and CD1c molecules and group 2 which includes CD1d molecules and their homologs in other species [2]

MOLECULAR MASS OF CD1 Family  

POST-TRANSCRIPTIONAL MODIFICATION OF CD1 Family  

• The alternative splicing pattern is tissue specific and gives rise to membrane attached and soluble forms
• Multiple splicing patterns have been found for all CD1 transcripts except for CD1b [9]
• CD1a: The most abundant mRNA contained the intron between the a3 and the transmembrane (TM) domains, resulting in a stop codon just downstream of the a3 domain (unspliced transcript). Biochemical studies demonstrated that a secretory form of CD1a was synthesized from this transcript. The second product represents the membrane isoform. The third transcript corresponds to a product where the a3 domain is spliced to the middle of the TM domain. Therefore, the resulting product does not include most of the hydrophobic segment required for membrane attachment and has been postulated as a possible cytoplasmic protein. On thymocytes, only the membrane isoform was detected. Activated peripheral blood lymphocytes expressed a particular pattern of alternative splicing different from the one found in thymus and the transfected cell line [M. Salomone, unpublished results]
• CD1b only revealed a single membrane RNA product
• CD1c: A similar three-band pattern was described in thymus and in the transfected cell line. The unspliced isoform is homologous to the secreted form of CD1a. A second product corresponds to the "correctly" spliced membrane form. The third product is slightly different from its equivalent of CD1a. Resting PBMC lack the unspliced product but is detected after PHA activation [unpublished results]. These results suggest that like CD1a, CD1c is also under development control
• CD1d-transfected cell line and thymocytes showed the presence of a single spliced membrane product. This product is absent on resting PBMC but was induced after 72 hr of PHA activation [M. Salomone, unpublished results]. CD1d expression on intestinal epithelial cells has also revealed different alternatively spliced products [6]. One transcript terminates in a cryptic polyadenylation site in the intron between a2 and a3 domains' exons. A second transcript deletes the TM region exon, and a third deletes the a3 domains' exon. It is currently unknown whether this transcript encodes functional proteins
• CD1e: A complex 5 bands splicing pattern was described for CD1e on resting PBMC, myeloid cell lines KG1a, HEL, THP1 and HL60, B cell lines Daudi and Raji, and in the pre-T cell lines MOLT-4. PHA activated PBMC express only a single high molecular transcript. [M. Salomone, unpublished results]

POST-TRANSLATIONAL MODIFICATION OF CD1 Family  

• The a1 and a2 domains contain the potential N-linked glycosylation sites, four in CD1a and in the product of CD1D, three in CD1b and CD1c, and two in the CD1e product.
• Differences between native and deglycosylated a chains suggests four oligosaccharide side chains of average size in CD1a and three in CD1c.

SUBSTRATES FOR CD1 Family   - No information

ENZYMES WHICH MODIFY CD1 Family   - No information

LIGANDS FOR CD1 Family AND MOLECULES ASSOCIATED WITH CD1 Family   - No information

• Expressed on cortical thymocytes (CD4+ CD8+) [2] and with less intensity on CD4+ and CD8+ thymocytes
• Absent on mature peripheral blood T cells but intracytoplasmic expression is detected on activated T lymphocytes [7]
• CD1c is expressed by a subset of peripheral blood B cells but CD1a and CD1b are not detected on normal B cells. However a proportion of B cell malignancies express CD1a, CD1b and CD1c isotypes[8]
• High levels of CD1a and less of CD1b and CD1c are present on Langerhans cells (LC). After migration from epidermis or in dendritic cells from the dermis, a high expression of CD1b and CD1c
• CD1a, CD1b and CD1c are detected in myeloid leukemias [8] These molecules are induced on monocytes by treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) alone or by GM-CSF plus Interleukin-4 (IL-4)
• CD1d gene products are expressed at low levels in the thymus. Immunoperoxidase staining with an anti-mouse CD1, which cross reacts with the human CD1d, demonstrated the cytoplasmic expression of this molecule on most epithelial cells in the large and small intestine [1]

• Homologous to histocompatibility antigens but not genetically linked to the histocompatibility locus
• The five CD1 genes are closely linked in a cluster mapping at chromosome 1q 22-23 [10]

SELECTION OF OTHER CD1 Family-SPECIFIC REFERENCE MAB   - No information

REVIEWS

1. Blumberg RS; Gerdes D; Chott A; Porcelli SA; Balk SP. Structure and function of the CD1 family of MHC-like cell surface proteins. Immunol. Rev. 1995 147:5 PubMed

2. Calabi, F, Yung Yu ,C, Bilsland,C A.G, and Milstein C. In: Immunogenetics of the mayor histocompatibility complex De. Srivastava, R, Ram, B, and Tyle, P. VCH Publishers, New York, 215-243, (1991)

3. Crispe IN; Mehal WZ. Strange brew: T cells in the liver. Immunol. Today 1996 17:522 PubMed

4. Melian A; Beckman EM; Porcelli SA; Brenner MB. Antigen presentation by CD1 and MHC-encoded class I-like molecules. Curr. Opin. Immunol. 1996 8:82 PubMed

PRIMARY CITATIONS

5. Bendelac A; Lantz O; Quimby ME; Yewdell JW; Bennink JR; Brutkiewicz RR. CD1 recognition by mouse NK1+ T lymphocytes. Science 1995 268:863 PubMed

6. Martin LH; Calabi F; Milstein C. Isolation of CD1 genes: a family of major histocompatibility complex-related differentiation antigens. Proc. Natl. Acad. Sci. U.S.A. 1986 83:9154 PubMed

7. Salamone MC; Fainboim L. Intracellular expression of CD1 molecules on PHA-activated normal T lymphocytes. Immunol. Lett. 1992 33:61 PubMed

8. Salamone MC; Roisman FR; Santiago J; Satz ML; Fainboim L. Analysis of CD1 molecules on haematological malignancies of myeloid and lymphoid origin. I. Cell surface antigen expression. Dis. Markers 1990 8:265 PubMed

9. Woolfson A; Milstein C. Alternative splicing generates secretory isoforms of human CD1. Proc. Natl. Acad. Sci. U.S.A. 1994 91:6683 PubMed

10. Yu CY; Milstein C. A physical map linking the five CD1 human thymocyte differentiation antigen genes. EMBO J. 1989 8:3727 PubMed

WWW RESOURCES

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Modified 10/14/99   mpr@mail.nih.gov