• Ber-H2 antigen
• Ki-1 antigen

MAJOR LINKS FOR CD30  

• NCBI LocusLink Record: 943
• Mendelian Inheritance in Man (OMIM): 153243
• SwissProt annotated protein record: P28908

CELLULAR FUNCTION OF CD30  

• Pleiotropic effects on CD30-positive lymphoma cell lines ranging from cell proliferation to cell death**
• Thought to be involved in negative selection of T-cells in the thymus*
• Involved in TCR-mediated cell death**
• Member of the TNFR family of molecules, activate NFkB through interaction with TRAF2 and TRAF5*
• Although thought at one time to represent a marker on TH2 cells, it has been also identified on TH0 and TH1 cells as well as (at lower levels) on CD8+ T-cells
• Overexpression of CD30v activates NFkB in Jurkat cells and induces NBT reduction activity in HL-60 cells**
• In the mouse crosslinking causes IL-5 production but not IFN gamma

DISEASE RELEVANCE OF CD30 AND FUNCTION OF CD30 IN INTACT ANIMAL  

• CD30 was originally identified as Ki-1, an antigen expressed on Reed-Sternberg cells in Hodgkin's lymphomas and other non-Hodgkin's lymphomas, particularly diffuse large-cell lymphoma and immunoblastic lymphoma
• Cutaneous lymphoproliferative disorders expressing CD30 include lymphomatoid papulosis, peripheral T-cell lymphomas and anaplastic large-cell lymphomas
• Expressed on lymphocytes infected with HIV, HTLV-1 or EBV*
• Crosslinking on HIV infected T-cells causes activation of latent HIV production
• Soluble levels of CD30 are elevated and associated with prognosis in Hodgkin's Disease and AIDS. Elevated levels were reported in patients with ATL and a part of those with non-Hodgkin's lymphoma**
• Most recently it has been found expressed on the primary effusion lymphoma and Castleman's disease associated with the recently identified herpes homines virus 8 (HHV8) or Kaposi's Sarcoma Herpes Virus*
• Elevated serum levels of soluble CD30 have also been identified in patients with hepatitis B infection, correlating with activity of disease

• Families in which CD30 is a member
  • CD30-->TNF-R

MOLECULAR STRUCTURE OF CD30  

• Type 1 glycoprotein with five (human) or three (murine and rat) cysteine-rich repeats with a central hinge sequence*
• The mouse and rat CD30 cDNA encodes 498 and 493 amino acid proteins, respectively which lack 90 amino acids found only in the human CD30, thought to be partially duplicated from one of the cysteine rich domains*
• Two sites of N-glycosylation are noted within the cysteine rich sequences

MOLECULAR MASS OF CD30  

POST-TRANSCRIPTIONAL MODIFICATION OF CD30  

• A variant form of CD30 (CD30v) having only the cytoplasmic domain is expressed in alveolar macrophages. CD30v mRNA is transcribed from an alternative promoter located in the intron

POST-TRANSLATIONAL MODIFICATION OF CD30  

• Soluble form of Mr 85,000 produced by metalloproteinase
• Constitutive phosphorylation**
• The hinge region and the area proximal to the membrane are likely O-glycosylated

• A cryptic promoter in the intron drives transcription of variant CD30 mRNA (see below)

SUBSTRATES FOR CD30   - No information

ENZYMES WHICH MODIFY CD30  

LIGANDS FOR CD30 AND MOLECULES ASSOCIATED WITH CD30  

• Note 1. The cytoplasmic tail of CD30 associate with TRAF1, 2, 3 and 5, but not with TRAF6 **

• Activated T lymphocytes
• Activated B lymphocytes
• Activated NK cells
• Monocytes
• Cell lines - HUT102, CEM, Jurkat, JY, MOLT4, NALM6, RPMI 8226, FLG 29.1, U937, and YT*
• Large lymphoid cells in lymph node, tonsil, thymus, decidua and endometrial cells with decidual change*
• Hodgkin's lymphoma; Reed-Sternberg cells, Hodgkin cells*
• Non-Hodgkin's lymphoma: Anaplastic large cell lymphoma (ALCL), pleomorphic (medium to large cell) and immunoblastic lymphoma
• Embryonal carcinoma, mixed germ cell tumor*

• Gene maps to 1p36 in humans and 5q36.2 in rats**
• The expression of this molecule is found on approximately 15% of CD45RO+ T-cells after activation and in man, appears to be the major subset producing gamma interferon. This is inducible with IL-12 and inhibited by IL-10 or antibodies to IL-2. Both CD30+ and CD30- cells respond to IL-2 following activation, but only the CD30 subset following IL-12 addition
• Considerable controversy about its precise role in delineating TH1 and TH2 subsets remains but the preponderance of data suggests that both subsets can express this molecule
• Stimulated splenocytes express most of the CD30 on CD8+ cells, peaking at 4-5 days

SELECTION OF OTHER CD30-SPECIFIC REFERENCE MAB  

REVIEWS

1. Del Prete G,Maggi E,Pizzolo G,Romagnani S CD30, Th2 cytokines and HIV infection: a complex and fascinating link. Immunol Today 1995 16:76 PubMed

2. Falini B,Pileri S,Pizzolo G,Durkop H,Flenghi L,Stirpe F,Martelli MF,Stein H CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood 1995 85:1 ** PubMed

3. de Bruin PC,Gruss HJ,van der Valk P,Willemze R,Meijer CJ CD30 expression in normal and neoplastic lymphoid tissue: biological aspects and clinical implications. Leukemia 1995 9:1620 PubMed

PRIMARY CITATIONS

4. Agrawal B,Reddish M,Longenecker BM CD30 expression on human CD8+ T cells isolated from peripheral blood lymphocytes of normal donors. J Immunol 1996 157:3229 PubMed

5. Aizawa S,Nakano H,Ishida T,Horie R,Nagai M,Ito K,Yagita H,Okumura K,Inoue J,Watanabe T Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation. J Biol Chem 1997 272:2042 ** PubMed

6. Aizawa S,Satoh H,Horie R,Ito K,Choi SH,Takeuchi H,Watanabe T Cloning and characterization of a cDNA for rat CD30 homolog and chromosomal assignment of the genomic gene. Gene 1996 182:155 ** PubMed

7. Alzona M,Jack HM,Fisher RI,Ellis TM IL-12 activates IFN-gamma production through the preferential activation of CD30+ T cells. J Immunol 1995 154:9 PubMed

8. Amakawa R,Hakem A,Kundig TM,Matsuyama T,Simard JJ,Timms E,Wakeham A,Mittruecker HW,Griesser H,Takimoto H,Schmits R,Shahinian A,Ohashi P,Penninger JM,Mak TW Impaired negative selection of T cells in Hodgkin's disease antigen Cell 1996 84:551 PubMed

9. Ansieau S,Scheffrahn I,Mosialos G,Brand H,Duyster J,Kaye K,Harada J,Dougall B,Hubinger G,Kieff E,Herrmann F,Leutz A,Gruss HJ Tumor necrosis factor receptor-associated factor (TRAF)-1, TRAF-2, and Proc Natl Acad Sci U S A 1996 93:14053 ** PubMed

10. Biswas P,Smith CA,Goletti D,Hardy EC,Jackson RW,Fauci AS Cross-linking of CD30 induces HIV expression in chronically infected T cells. Immunity 1995 2:587 PubMed

11. Bowen MA,Lee RK,Miragliotta G,Nam SY,Podack ER Structure and expression of murine CD30 and its role in cytokine production. J Immunol 1996 156:442 PubMed

12. Del Prete G,De Carli M,D'Elios MM,Daniel KC,Almerigogna F,Alderson M,Smith CA,Thomas E,Romagnani S CD30-mediated signaling promotes the development of human T helper type 2-like T cells. J Exp Med 1995 182:1655 PubMed

13. Duckett CS,Gedrich RW,Gilfillan MC,Thompson CB Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol Cell Biol 1997 17:1535 ** PubMed

14. Gedrich RW,Gilfillan MC,Duckett CS,Van Dongen JL,Thompson CB CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins. J Biol Chem 1996 271:12852 PubMed

15. Hamann D,Hilkens CM,Grogan JL,Lens SM,Kapsenberg ML,Yazdanbakhsh M,van Lier RA CD30 expression does not discriminate between human Th1- and Th2-type T cells. J Immunol 1996 156:1387 PubMed

16. Horie R,Ito K,Tatewaki M,Nagai M,Aizawa S,Higashihara M,Ishida T,Inoue J,Takizawa H,Watanabe T A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and is expressed in alveolar macrophages. Blood 1996 88:2422 ** PubMed

17. Lee SY,Park CG,Choi Y T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors. J Exp Med 1996 183:669 PubMed

18. Nador RG,Cesarman E,Chadburn A,Dawson DB,Ansari MQ,Sald J,Knowles DM Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 1996 88:645 PubMed

19. Wiley SR,Goodwin RG,Smith CA Reverse signaling via CD30 ligand. J Immunol 1996 157:3635 PubMed

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Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov