Alternative titles; symbols
HGNC Approved Gene Symbol: CD27
Cytogenetic location: 12p13.31 Genomic coordinates (GRCh38): 12:6,443,892-6,451,713 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12p13.31 | Lymphoproliferative syndrome 2 | 615122 | Autosomal recessive | 3 |
CD27 is a member of the tumor necrosis factor receptor (TFNR) superfamily. These receptors play an important role in cell growth and differentiation, as well as in apoptosis or programmed cell death. The homology of the TNFR gene superfamily is restricted to the extracellular region of the family members and is characterized by the presence of a Cys knot motif, which occurs 3 times in CD27 (summary by Prasad et al., 1997).
Using the leukemic cells of a patient with Sezary syndrome as an immunogen, Bigler et al. (1988) developed a monoclonal antibody, designated S152, that reacted with the leukemic cells and a subset of circulating T lymphocytes. When cells were activated by mitogens or alloantigens, the intensity of staining by the monoclonal antibody S152 increased to more than 6 times that seen on resting cells. Bigler et al. (1988) demonstrated that CD27 is a disulfide-linked homodimer. It appeared to play a functional role during T-cell activation.
CD27 is a glycosylated, type I transmembrane protein of about 55 kD and exists as homodimers with a disulfide bridge linking the 2 monomers. The disulfide bridge is in the extracellular domain close to the membrane. The ligand for CD27 is CD70 (602840), which belongs to the tumor necrosis factor (TNF) family of ligands. Unlike CD27, CD70 is a type II transmembrane protein with an apparent molecular mass of 50 kD. Because of CD70's homology to TNF-alpha (TNFA; 191160) and to TNF-beta (TNFB; 153440), CD70 was predicted to have a trimeric structure made up of 3 identical subunits, possibly interacting with 3 CD27 homodimers (summary by Prasad et al., 1997).
Baens et al. (1995) isolated a large number of cDNAs by direct cDNA selection using pools of human chromosome 12p cosmids. STSs were developed for all cosmids, among them, a polymorphic simple sequence repeat associated with CD27. Regional assignment of the STSs by PCR analysis with somatic cell hybrids and fluorescence in situ hybridization showed that they map to 12p13.
Prasad et al. (1997) showed that CD27, expressed on discrete subpopulations of T and B cells and known to provide costimulatory signals for T- and B-cell proliferation and B-cell immunoglobulin production, can also induce apoptosis. Using the yeast 2-hybrid system, Prasad et al. (1997) cloned a novel human protein, designated Siva (605567), that binds to the CD27 cytoplasmic tail. Overexpression of Siva in various cell lines induced apoptosis, suggesting an important role of Siva in the CD27-transduced apoptotic pathway.
Using antibody blocking studies, Carr et al. (2006) showed that Cd70 ligation of Cd27 on T-cell receptor (TCR)-stimulated mouse Cd8 (see 186910)-positive T cells caused their expansion in the absence of Il2r (147730) stimulation. Flow cytometric proliferation analysis revealed that Cd27 ligation on TCR-stimulated Cd8-positive T cells promoted cell survival by maintaining Il7ra (146661) expression. Expansion of Cd8-positive T cells was not associated with differentiation to Ifng (147570) expression or cytotoxic T-lymphocyte function, and increased concentration of Il2 (147680) was required to induce Ifng production by Cd27-ligated cells. Carr et al. (2006) proposed that TCR/CD27 stimulation enables CD8-positive T cells to replicate and contribute to the continuous generation of new effector cells in persistent viral infection.
In 2 Moroccan brothers, born of consanguineous parents, with lymphoproliferative syndrome-2 (LPFS2; 615122), van Montfrans et al. (2012) identified a homozygous truncating mutation in the CD27 gene (W8X; 186711.0001). The CD27 gene was studied because flow cytometric analysis during diagnostic work-up showed absence of CD27 on all patient lymphocytes. CD27 is recognized as a marker for memory B cells and is considered of diagnostic value in patients who have decreased numbers of switched memory B cells. Both brothers presented in early childhood with lymphadenopathy, fever, and hepatosplenomegaly associated with EBV infection. Both had an immunodeficiency associated with hypogammaglobulinemia and impaired T cell-dependent B-cell activation, as well as a subtle defect in CD8+ T-cell function. One patient responded well to immunoglobulin therapy and showed prolonged survival to age 21 years; the other patient died of aplastic anemia in childhood.
In 8 affected individuals from 3 unrelated families with LPFS2, Salzer et al. (2013) identified the same homozygous mutation in the CD27 gene (C53Y; 186711.0002). The mutation was identified by exome sequencing in 1 family and confirmed by Sanger sequencing in all families. The phenotype varied significantly even within the same family. Some mutation carriers were asymptomatic with borderline-low hypogammaglobulinemia, whereas others had a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation.
The TRAF (TNFR-associated factor)-linked members of the TNFR superfamily, such as CD27, CD30 (153243), and OX40 (600315), are exclusively expressed on cells of the lymphoid lineage, usually in an activation-specific manner, and all enhance T-cell receptor-induced T-cell expansion. CD27 is expressed on NK-, T-, and B-cell populations. By analysis of responses to influenza virus in Cd27-deficient mice, Hendriks et al. (2000) determined that CD27 is essential for adequate expansion of CD4- and CD8-positive T cells, particularly in the lung, in response to primary infection. The memory T-cell response was delayed in Cd27-deficient mice as compared with that in wildtype mice. However, the lack of Cd27 did not affect cytolytic T-cell function or the B-cell response to influenza virus. Indeed, Cd27-deficient mice did not become more ill than wildtype mice and recovered from influenza in the same time period as wildtype mice.
In 2 Moroccan brothers, born of consanguineous parents, with autosomal recessive lymphoproliferative syndrome-2 (LPFS2; 615122), van Montfrans et al. (2012) identified a homozygous 24G-A transition in the CD27 gene, resulting in a trp8-to-ter (W8X) substitution. Each unaffected parent was heterozygous for the mutation. The CD27 gene was studied because flow cytometric analysis during diagnostic work-up showed absence of CD27 on all patient lymphocytes. CD27 is recognized as a marker for memory B cells and is considered of diagnostic value in patients who have decreased numbers of switched memory B cells. Both brothers presented in early childhood with lymphadenopathy, fever, and hepatosplenomegaly associated with EBV infection. Both had an immunodeficiency associated with hypogammaglobulinemia and impaired T cell-dependent B-cell activation, as well as a subtle defect in CD8+ T-cell function. One patient responded well to immunoglobulin therapy and showed prolonged survival to age 21 years; the other patient died of aplastic anemia in childhood.
In 8 affected individuals from 3 unrelated families with lymphoproliferative syndrome-2 (LPFS2; 615122), Salzer et al. (2013) identified the same homozygous 158G-A transition in the CD27 gene, resulting in a cys53-to-tyr (C53Y) substitution at a conserved residue in a motif of the ligand-binding domain. The mutation was identified by exome sequencing in 1 family and confirmed by Sanger sequencing in all families. The phenotype varied significantly even within the same family. Some mutation carriers were asymptomatic with borderline-low hypogammaglobulinemia, whereas others had a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation.
Baens, M., Aerssens, J., Van Zand, K., Van den Berghe, H., Marynen, P. Isolation and regional assignment of human chromosome 12p cDNAs. Genomics 29: 44-52, 1995. [PubMed: 8530100] [Full Text: https://doi.org/10.1006/geno.1995.1213]
Bigler, R. D., Bushkin, Y., Chiorazzi, N. S152 (CD27): a modulating disulfide-linked T cell activation antigen. J. Immun. 141: 21-28, 1988. [PubMed: 2837508]
Carr, J. M., Carrasco, M. J., Thaventhiran, J. E. D., Bambrough, P. J., Kraman, M., Edwards, A. D., Al-Shamkhani, A., Fearon, D. T. CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation. Proc. Nat. Acad. Sci. 103: 19454-19459, 2006. [PubMed: 17159138] [Full Text: https://doi.org/10.1073/pnas.0609706104]
Hendriks, J., Gravestein, L. A., Tesselaar, K., van Lier, R. A. W., Schumacher, T. N. M., Borst, J. CD27 is required for generation and long-term maintenance of T cell immunity. Nature Immun. 1: 433-440, 2000. [PubMed: 11062504] [Full Text: https://doi.org/10.1038/80877]
Prasad, K. V. S., Ao, Z., Yoon, Y., Wu, M. X., Rizk, M., Jacquot, S., Schlossman, S. F. CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein. Proc. Nat. Acad. Sci. 94: 6346-6351, 1997. [PubMed: 9177220] [Full Text: https://doi.org/10.1073/pnas.94.12.6346]
Salzer, E., Daschkey, S., Choo, S., Gombert, M., Santos-Valente, E., Ginzel, S., Schwendinger, M., Haas, O. A., Fritsch, G., Pickl, W. F., Forster-Waldl, E., Borkhardt, A., Boztug, K., Bienemann, K., Seidel, M. G. Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. Haematologica 98: 473-478, 2013. [PubMed: 22801960] [Full Text: https://doi.org/10.3324/haematol.2012.068791]
van Montfrans, J. M., Hoepelman, A. I. M., Otto, S., van Gijn, M., van de Corput, L., de Weger, R. A., Monaco-Shawver, L., Banerjee, P. P., Sanders, E. A. M., Jol-van der Zijde, C. M., Betts, M. R., Orange, J. S., Bloem, A. C., Tesselaar, K. CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J. Allergy Clin. Immun. 129: 787-793, 2012. [PubMed: 22197273] [Full Text: https://doi.org/10.1016/j.jaci.2011.11.013]