Functional topography of discrete domains of human CD38

C. M. Ausiello, F. Urbani, R. Lande, A. La Sala, B. Di Carlo, G. Baj, N. Surico, J. Hilgers, S. Deaglio, A. Funaro, F. Malavasi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In addition to its catalytic activities as ecto-NAD + glycohydrolase (NADase), CD38 displays the ability to transduce signals of biological relevance. Indeed, ligation of CD38 on peripheral blood mononuclear cells (PBMC) by agonistic monoclonal antibodies (mAbs) is followed by the transcription and secretion of a vast array of regulatory cytokines. The present work addresses the issue of whether the signals leading to calcium (Ca 2+) mobilization, lymphocyte proliferation and release of cytokines is dependent on the epitopes recognized by the individual mAbs. Competition binding analysis identifies two families of mAbs, namely IB4, IB6 and AT2 on one side and OKT10, SUN-4B7 and AT1 on the other. Each mAb family binds epitopes that are completely or partially common. However, the functional activities of the CD38 molecule can not be simply attributed to the epitopes engaged: for instance, IB4 and OKT10 mAbs, which bind different epitopes, perform as agonistic mAbs in inducing PBMC proliferation and interferon (IFN)-γ secretion. SUN-4B7 yields intermediate effects, whereas IB6, AT1 and AT2 mAbs are totally ineffective. The effects mediated by IB4 and OKT10 mAbs are apparent in 80% of the healthy individuals studied, whereas the effects of SUN-4B7 mAb operate only in 25% of the donors. Intedeukin (IL)-6 secretion was observed in all individuals analyzed, irrespective of the epitopes triggered and of mAbs used to ligate the CD38 molecule. In addition, IB4 is the only mAb able to induce significant intracellular Ca 2+ fluxes.

Original languageEnglish
Pages (from-to)539-547
Number of pages9
JournalTissue Antigens
Volume56
Issue number6
DOIs
Publication statusPublished - 2000

Fingerprint

Topography
Monoclonal Antibodies
Epitopes
Blood Cells
Blood
NAD+ Nucleosidase
Cytokines
Molecules
Lymphocytes
Cell proliferation
Transcription
Interferons
Ligation
Interleukin-6
Catalyst activity
Cell Proliferation
Fluxes
Calcium

Keywords

  • Ca fluxes
  • CD38
  • Cytokines
  • Human peripheral blood mononuclear cells
  • IFN-γ
  • IL-6
  • Proliferation
  • Signal transduction

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Ausiello, C. M., Urbani, F., Lande, R., La Sala, A., Di Carlo, B., Baj, G., ... Malavasi, F. (2000). Functional topography of discrete domains of human CD38. Tissue Antigens, 56(6), 539-547. https://doi.org/10.1034/j.1399-0039.2000.560608.x

Functional topography of discrete domains of human CD38. / Ausiello, C. M.; Urbani, F.; Lande, R.; La Sala, A.; Di Carlo, B.; Baj, G.; Surico, N.; Hilgers, J.; Deaglio, S.; Funaro, A.; Malavasi, F.

In: Tissue Antigens, Vol. 56, No. 6, 2000, p. 539-547.

Research output: Contribution to journalArticle

Ausiello, CM, Urbani, F, Lande, R, La Sala, A, Di Carlo, B, Baj, G, Surico, N, Hilgers, J, Deaglio, S, Funaro, A & Malavasi, F 2000, 'Functional topography of discrete domains of human CD38', Tissue Antigens, vol. 56, no. 6, pp. 539-547. https://doi.org/10.1034/j.1399-0039.2000.560608.x
Ausiello CM, Urbani F, Lande R, La Sala A, Di Carlo B, Baj G et al. Functional topography of discrete domains of human CD38. Tissue Antigens. 2000;56(6):539-547. https://doi.org/10.1034/j.1399-0039.2000.560608.x
Ausiello, C. M. ; Urbani, F. ; Lande, R. ; La Sala, A. ; Di Carlo, B. ; Baj, G. ; Surico, N. ; Hilgers, J. ; Deaglio, S. ; Funaro, A. ; Malavasi, F. / Functional topography of discrete domains of human CD38. In: Tissue Antigens. 2000 ; Vol. 56, No. 6. pp. 539-547.
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