Alternative titles; symbols
HGNC Approved Gene Symbol: CD2
Cytogenetic location: 1p13.1 Genomic coordinates (GRCh38): 1:116,754,430-116,769,229 (from NCBI)
CD2 is a surface antigen of the human T-lymphocyte lineage that is expressed on all peripheral blood T cells. It is one of the earliest T-cell markers, being present on more than 95% of thymocytes; it is also found on some natural killer cells but not on B lymphocytes. Monoclonal antibodies directed against CD2 inhibit the formation of rosettes with sheep erythrocytes, indicating that CD2 is the erythrocyte receptor or is closely associated with it (summary by Sewell et al., 1986).
Sewell et al. (1986) isolated cDNA clones for CD2 by screening an expression library with antiserum against the purified denatured antigen. The predicted 327-amino acid sequence of the CD2 antigen was found to have features of a transmembrane glycoprotein, with distant similarity to the immunoglobulin supergene family, and an extensive, proline-rich, basic cytoplasmic domain. Seed and Aruffo (1987) also cloned a cDNA for CD2. They used a highly efficient technique based on transient expression in COS cells and adherence of cells expressing surface antigen to antibody-coated dishes, a process they called panning.
Diamond et al. (1988) concluded from genomic DNA clones that the human T11 gene is about 12 kb long and has 5 exons. The organization of the murine and human T11 genes is very similar.
Lang et al. (1988) found that in transgenic mice a 28.5-kb segment of DNA, consisting of 4.5 kb of 5-prime flanking sequences, 15 kb containing 5 exons, and 9 kb of 3-prime flanking sequences, can direct the expression of CD2 only on thymocytes, circulating T cells, and megakaryocytes. Using a baculoviral expression system to produce milligram quantities of the hydrophilic extracellular segment of CD2, Richardson et al. (1988) demonstrated that the domain involved in cellular adhesion is encoded by a single 321-basepair exon.
Brown et al. (1987) used a cDNA clone as a probe to define the chromosomal location of CD2. Southern blot analysis of genomic DNA from somatic cell hybrids showed a high degree of concordance for human chromosome 1. In particular, a hybrid that contained the short arm only of human chromosome 1 was positive. The localization of CD2 to 1p13 was established by in situ hybridization. By Southern blotting of DNA from a panel of somatic cell hybrids, Clayton et al. (1988) assigned the CD2 gene to human chromosome 1 and murine chromosome 3. Based on the homology between murine chromosome 3 and human chromosome 1, they hypothesized that the human CD2 homolog lies on the short arm of chromosome 1, proximal to p22.1. By fluorescence in situ hybridization, Mitchell et al. (1995) mapped CD2 to 1p13.1.
Kingsmore et al. (1989) demonstrated physical linkage of CD2 and its ligand, LFA3 (153420).
Locus control regions (LCRs) direct high-level and tissue-specific expression of linked genes in transgenic mice. Festenstein et al. (1996) stated that this expression is independent of site of integration in the host genome. With the use of transgenic mice, such an LCR was identified within the 3-prime flanking region of the human CD2 gene. Festenstein et al. (1996) found that transgenic mice carrying a human CD2 minigene attached only to the 3-prime CD2 transcriptional enhancer exhibited variegated expression when the transgene integrated in the centromere. The phenotype was similar to position effect variegation (VEV) as described in Drosophila and Saccharomyces, in which the cell-to-cell variation of gene expression within a cell lineage is correlated with the translocation of a normally euchromatic gene to centromeric heterochromatin. In contrast, the authors found that mice carrying a transgene with additional 3-prime sequence showed no variegation even when the transgene integrated in centromeric positions. Their result suggested that LCRs operate by ensuring an open chromatin configuration and that a short region, with no enhancer activity, functions in the establishment, maintenance, or both of an open chromatin domain.
Crystal Structure
Interaction between CD2 and its counterreceptor, LFA3 (CD58), on opposing cells optimizes immune recognition, facilitating contacts between helper T lymphocytes and antigen-presenting cells as well as between cytolytic effectors and target cells. Wang et al. (1999) reported the crystal structure of the heterophilic adhesion complex between the N-terminal domains of human CD2 and CD58 at more than 3.2-angstrom resolution. A strikingly asymmetric, orthogonal, face-to-face interaction involving the major beta sheets of the respective immunoglobulin-like domains with poor shape complementarity was revealed. These features explained CD2-CD58 dynamic binding, offering insights into the interactions of related immunoglobulin superfamily receptors.
Brown, M. H., Gorman, P. A., Sewell, W. A., Spurr, N. K., Sheer, D., Crumpton, M. J. The gene coding for the human T-lymphocyte CD2 antigen is located on chromosome 1p. Hum. Genet. 76: 191-195, 1987. [PubMed: 3111975] [Full Text: https://doi.org/10.1007/BF00284920]
Clayton, L. K., Ramachandran, H., Pravtcheva, D., Chen, Y.-F., Diamond, D. J., Ruddle, F. H., Reinherz, E. L. The gene for T11 (CD2) maps to chromosome 1 in humans and to chromosome 3 in mice. J. Immun. 140: 3617-3621, 1988. [PubMed: 2896210]
Diamond, D. J., Clayton, L. K., Sayre, P. H., Reinherz, E. L. Exon-intron organization and sequence comparison of human and murine T11 (CD2) genes. Proc. Nat. Acad. Sci. 85: 1615-1619, 1988. [PubMed: 2894031] [Full Text: https://doi.org/10.1073/pnas.85.5.1615]
Festenstein, R., Tolaini, M., Corbella, P., Mamalaki, C., Parrington, J., Fox, M., Miliou, A., Jones, M., Kioussis, D. Locus control region function and heterochromatin-induced position effect variegation. Science 271: 1123-1125, 1996. [PubMed: 8599090] [Full Text: https://doi.org/10.1126/science.271.5252.1123]
Kingsmore, S. F., Watson, M. L., Moseley, W. S., Seldin, M. F. Physical linkage of genes encoding the lymphocyte adhesion molecules CD2 and its ligand LFA-3. Immunogenetics 30: 123-125, 1989. [PubMed: 2474492] [Full Text: https://doi.org/10.1007/BF02421541]
Lang, G., Wotton, D., Owen, M. J., Sewell, W. A., Brown, M. H., Mason, D. Y., Crumpton, M. J., Kioussis, D. The structure of the human CD2 gene and its expression in transgenic mice. EMBO J. 7: 1675-1682, 1988. [PubMed: 2901953] [Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb02995.x]
Mitchell, E. L. D., Jones, D., White, G. R. M., Varley, J. M., Santibanez Koref, M. F. Determination of the gene order of the three loci CD2, NGFB, and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridization. Cytogenet. Cell Genet. 70: 183-185, 1995. Note: Erratum: Cytogenet. Cell Genet. 71: 306 only, 1995. [PubMed: 7789166] [Full Text: https://doi.org/10.1159/000134028]
Richardson, N. E., Chang, H.-C., Brown, N. R., Hussey, R. E., Sayre, P. H., Reinherz, E. L. Adhesion domain of human T11 (CD2) is encoded by a single exon. Proc. Nat. Acad. Sci. 85: 5176-5180, 1988. [PubMed: 2455894] [Full Text: https://doi.org/10.1073/pnas.85.14.5176]
Seed, B., Aruffo, A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc. Nat. Acad. Sci. 84: 3365-3369, 1987. [PubMed: 2437578] [Full Text: https://doi.org/10.1073/pnas.84.10.3365]
Sewell, W. A., Brown, M. H., Dunne, J., Owen, M. J., Crumpton, M. J. Molecular cloning of the human T-lymphocyte surface CD2 (T11) antigen. Proc. Nat. Acad. Sci. 83: 8718-8722, 1986. Note: Erratum: Proc. Nat. Acad. Sci. 84: 7256 only, 1987. [PubMed: 3490670] [Full Text: https://doi.org/10.1073/pnas.83.22.8718]
Wang, J., Smolyar, A., Tan, K., Liu, J., Kim, M., Sun, Z. J., Wagner, G., Reinherz, E. L. Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors. Cell 97: 791-803, 1999. [PubMed: 10380930] [Full Text: https://doi.org/10.1016/s0092-8674(00)80790-4]