Alternative titles; symbols
HGNC Approved Gene Symbol: CD1A
Cytogenetic location: 1q23.1 Genomic coordinates (GRCh38): 1:158,248,336-158,258,269 (from NCBI)
CD1 is a family of nonpolymorphic genes that encode major histocompatibility complex (MHC; see 142800)-like glycoproteins that present lipid and glycolipid antigens to T cells. CD1A is 1 of 5 distinct CD1 genes that are variably conserved in different mammalian species. These CD1 genes can be separated into 2 groups on the basis of sequence homology. Group 1 includes CD1A, CD1B (188360), CD1C (188340), and CD1E (188411), which are present in human and some other mammals, but are absent in mouse and rat. Group 2 includes only CD1D (188410), which has been found in all mammalian species studied (review by Park and Bendelac, 2000).
Calabi and Milstein (1986) noted that CD1 antigens were thought to be human counterparts of mouse thymus leukemia (TL) antigens (188850). Like TL antigens, CD1 antigens are expressed on cortical thymocytes, as well as on some lymphoid neoplasias, and resemble in structure MHC class I antigens. Calabi and Milstein (1986) isolated cDNA clones encoding a CD1 antigen. These clones revealed a novel family of genes which are MHC related but are neither equivalent to mouse TL antigens nor linked to the MHC.
Martin et al. (1986) isolated 5 CD1 genes from a human genomic library. They found that all share a highly conserved exon that encodes a domain homologous to the beta-2-microglobulin (B2M; 109700)-binding domain of MHC class I antigens.
Martin et al. (1987) reported the genomic coding sequences for 3 of the CD1 genes and identified them as CD1A, CD1B, and CD1C using DNA transfection assays. Balk et al. (1989) isolated and characterized a gene coding for a fourth CD1 molecule, CD1D. Sequence similarities of the CD1 molecules and the class I MHC molecules were pointed out.
By study of mouse-human somatic hybrids that contained human chromosome 6 and expressed HLA, Calabi and Milstein (1986) observed a pattern of independent segregation of CD1 and MHC. Preliminary experiments suggested that the CD1 genes map to chromosome 1.
Albertson et al. (1988) devised a technique for high resolution cytologic mapping of genes in the human by adapting a method for in situ hybridization that was originally developed for mapping genes in the nematode, Caenorhabditis elegans. The probe DNAs were labeled by incorporation of biotin dUTP and the site of hybridization detected by immunofluorescence. The bands on the chromosomes were visualized by staining with Hoechst 33258, a heterologous ribosomal DNA (rDNA) probe. These rDNA signals, mapping to acrocentric chromosomes, were used as fiducial markers when aligning the 2 fluorescent images. By this method, Albertson et al. (1988) assigned the thymocyte CD1 antigen genes to human chromosome 1q22-q23. They suggested that the technique permits mapping of cloned DNAs to a 10-Mb region. They commented that the fluorescent method has several advantages over bright-field techniques: first, chromosome bands may be obtained without pretreatment of cell cultures or chromosome spreads; second, it is not necessary to preband; and third, the hybridization signals are distinctive, making it possible to resolve hybridization to individual chromatids.
Yu and Milstein (1989) established the close physical linkage of the 5 CD1 genes, which are encompassed in a 190-kb segment of DNA. The order of the genes is CD1D--CD1A--CD1C--CD1B--CD1E. With the exception of CD1B, they are all in the same transcriptional orientation. They are evenly spaced in the complex except for the distance between CD1D and CD1A, which is 2 to 3 times greater than the average.
In the course of constructing a physical map of human 1q21-q23, Oakey et al. (1992) determined that the CD1A gene is located in the centromeric portion of this segment, proximal to CRP (123260). CD1B, CD1C, and CD1D are in the same vicinity.
Moseley et al. (1989) demonstrated that the mouse homolog of CD1, Ly38, maps to mouse chromosome 3.
Park and Bendelac (2000) reviewed CD1 lipid antigen presentation. They noted that the crystal structure of murine Cd1d (see Zeng et al., 1997), showing a deep ligand-binding groove made of 2 large electrostatically neutral pockets lined with clustered hydrophobic residues, appears to suggest a way in which CD1 molecules, which complex with B2M, bind lipids. Park and Bendelac (2000) also observed that the stable lipid binding might occur in the secretory pathway, at the cell surface, or only after internalization in an acidified compartment. The intracellular locations include different compartments of the endocytic pathway: CD1A is concentrated in the early or recycling endosome, CD1B and CD1D in the late endosome or lysosome, and CD1C in the late endosome. Access to the endocytic pathway is regulated by a tyrosine-based motif in the cytoplasmic tail of CD1 that differs among CD1B, CD1C, and CD1D.
Vincent et al. (2002) showed that group-1 (i.e., CD1A, CD1B, and CD1C) foreign antigen-nonspecific CD1-restricted T-cell clones could promote dendritic cell (DC) maturation in the presence of lipopolysaccharide and gamma-interferon (IFNG; 147570), whereas group-2 (i.e., CD1D)-restricted T cells failed to induce interleukin-12 p70 (IL12; see 161561) production and DC maturation except in the presence of CD40 ligand (CD40LG; 300386). On the other hand, the CD1D-restricted T-cell clones were more efficient producers of IL10 (124092).
Moody et al. (2004) reported that CD1A presents to T cells a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T-cell activation was mediated by the alpha-beta T-cell receptors and was specific for structure of the acyl and peptidic components of these antigens. Moody et al. (2004) concluded that their studies identified a means of intracellular pathogen detection and identified lipopeptides as a biochemical class of antigens for T cells which, like conventional peptides, have a potential for marked structural diversity.
Van den Elzen et al. (2005) defined the pathways mediating markedly efficient exogenous lipid antigen delivery by apolipoproteins to achieve T-cell activation. Apolipoprotein E (107741) binds lipid antigens and delivers them by receptor-mediated uptake into endosomal compartments containing CD1 in antigen-presenting cells. Apolipoprotein E mediates the presentation of serum-borne lipid antigens and can be secreted by antigen-presenting cells as a mechanism to survey the local environment to capture antigens or to transfer microbial lipids from infected cells to bystander antigen-presenting cells. Thus, van den Elzen et al. (2005) concluded that the immune system has co-opted a component of lipid metabolism to develop immunologic responses to lipid antigens.
CD in the nomenclature of these cell surface antigens is derived from 'cluster of differentiation.' The expression of surface markers correlates with the stage of differentiation of lymphocytes, hence they were referred to as differentiation markers and proved to be powerful tools for identification, characterization, and analysis. The concept of differentiation markers, although derived from studies on lymphocytes, has greater applicability. For example, the developing embryo has stage-specific markers, and many other developing systems can be studied by using unique markers at certain stages of differentiation. Monoclonal antibodies facilitated greatly the identification of lymphocyte differentiation antigens; they also brought about a Tower of Babel in nomenclature as discoverers of new markers gave them new names without regard to possible identity to previously described antigens. In 1982, the First International Workshop in Human Leukocyte Differentiation Antigens was held in Paris. At that meeting, 139 monoclonal antibodies were tested by immunofluorescence, and the antibodies were grouped into 'clusters' on the basis of the results. At the Fifth International Congress of Immunology, held in Kyoto, Japan, in 1983, the nomenclature subcommittee officially adopted this scheme of nomenclature. The idea of the 'cluster of differentiation' was to group all known antibodies that reacted with the same marker. When new antigens are discovered, they are sometimes said to be 'clustered' when their relationship to other CDs has been determined.
Albertson, D. G., Fishpool, R., Sherrington, P., Nacheva, E., Milstein, C. Sensitive and high resolution in situ hybridization to human chromosomes using biotin labelled probes: assignment of the human thymocyte CD1 antigen genes to chromosome 1. EMBO J. 7: 2801-2805, 1988. [PubMed: 3053166] [Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb03135.x]
Balk, S. P., Bleicher, P. A., Terhorst, C. Isolation and characterization of a cDNA and gene coding for a fourth CD1 molecule. Proc. Nat. Acad. Sci. 86: 252-256, 1989. [PubMed: 2463622] [Full Text: https://doi.org/10.1073/pnas.86.1.252]
Calabi, F., Milstein, C. A novel family of human major histocompatibility complex-related genes not mapping to chromosome 6. Nature 323: 540-543, 1986. [PubMed: 3093894] [Full Text: https://doi.org/10.1038/323540a0]
Martin, L. H., Calabi, F., Lefebvre, F.-A., Bilsland, C. A. G., Milstein, C. Structure and expression of the human thymocyte antigens CD1a, CD1b, and CD1c. Proc. Nat. Acad. Sci. 84: 9189-9193, 1987. [PubMed: 2447586] [Full Text: https://doi.org/10.1073/pnas.84.24.9189]
Martin, L. H., Calabi, F., Milstein, C. Isolation of CD1 genes: a family of major histocompatibility complex-related differentiation antigens. Proc. Nat. Acad. Sci. 83: 9154-9158, 1986. [PubMed: 3097645] [Full Text: https://doi.org/10.1073/pnas.83.23.9154]
Moody, D. B., Young, D. C., Cheng, T.-Y., Rosat, J.-P., Roura-mir, C., O'Connor, P. B., Zajonc, D. M., Walz, A., Miller, M. J., Levery, S. B., Wilson, I. A., Costello, C. E., Brenner, M. B. T cell activation by lipopeptide antigens. Science 303: 527-531, 2004. Note: Erratum: Science 304: 211 only, 2004. [PubMed: 14739458] [Full Text: https://doi.org/10.1126/science.1089353]
Moseley, W. S., Watson, M. L., Kingsmore, S. F., Seldin, M. F. CD1 defines conserved linkage group border between human chromosomes 1 and mouse chromosomes 1 and 3. Immunogenetics 30: 378-382, 1989. [PubMed: 2478463] [Full Text: https://doi.org/10.1007/BF02425278]
Oakey, R. J., Watson, M. L., Seldin, M. F. Construction of a physical map on mouse and human chromosome 1: comparison of 13 Mb of mouse and 11 Mb of human DNA. Hum. Molec. Genet. 1: 613-620, 1992. [PubMed: 1301170] [Full Text: https://doi.org/10.1093/hmg/1.8.613]
Park, S.-H., Bendelac, A. CD1-restricted T-cell responses and microbial infection. Nature 406: 788-792, 2000. [PubMed: 10963609] [Full Text: https://doi.org/10.1038/35021233]
van den Elzen, P., Garg, S., Leon, L., Brigl, M., Leadbetter, E. A., Gumperz, J. E., Dascher, C. C., Cheng, T.-Y., Sacks, F. M., Illarionov, P. A., Besra, G. S., Kent, S. C., Moody, D. B., Brenner, M. B. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature 437: 906-910, 2005. [PubMed: 16208376] [Full Text: https://doi.org/10.1038/nature04001]
Vincent, M. S., Leslie, D. S., Gumperz, J. E., Xiong, X., Grant, E. P., Brenner, M. B. CD1-dependent dendritic cell instruction. Nature Immun. 3: 1163-1168, 2002. [PubMed: 12415264] [Full Text: https://doi.org/10.1038/ni851]
Yu, C. Y., Milstein, C. A physical map linking the five CD1 human thymocyte differentiation antigen genes. EMBO J. 8: 3727-3732, 1989. [PubMed: 2583117] [Full Text: https://doi.org/10.1002/j.1460-2075.1989.tb08548.x]
Zeng, Z.-H., Castano, A. R., Segelke, B. W., Stura, E. A., Peterson, P. A., Wilson, I. A. Crystal structure of mouse CD1: an MHC-like fold with a large hydrophobic binding groove. Science 277: 339-345, 1997. [PubMed: 9219685] [Full Text: https://doi.org/10.1126/science.277.5324.339]