NKG2D and natural cytotoxicity receptors are involved in natural killer cell interaction with self-antigen presenting cells and stromal cells

Alessandro Poggi, Claudia Prevosto, Marta Zancolli, Paolo Canevali, Alessandra Musso, Maria Raffaella Zocchi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

21 Citations (Scopus)

Abstract

It is thought that human natural killer (NK) lymphocytes should not damage self-tissues due to the inhibiting signal initiated by the engagement of one or another inhibitory receptor superfamily (IRS) members with self-human histocompatibility antigen (HLA)-I. During viral infection, the low expression of self-HLA-I on infected-cells leads to a reduction of the inhibiting signal and thus NK cells kill self-cells (missing self-hypothesis). Here, we have analyzed human NK cell interaction with self-cells as antigen-presenting cells (APC) or stromal cells isolated frombone marrowor skin. Despite the expression of high levels of HLA-I, APC and stromal cells are killed by interleukin (IL)-2-activated NK cells upon lymphocyte function antigen (LFA)1-(intracellular adhesion molecule) (ICAM)1 interaction. The natural cytotoxicity receptors NKp30 and NKp46 are responsible for the delivery of lethal hit to APC, whereas NKG2D-activating receptor, the ligand of the major histocompatibility complex (MHC)-related molecule MICA, and the UL16-binding protein are involved in stromal cell killing. These events are dependent on the activation of phosphoinositol 3-kinase and consequent release of perforins and granzymes. Both bone marrow stromal cells and skin fibroblasts inhibit T cell proliferation to alloantigen or triggering through CD3/T cell receptor complex. Importantly, NK cells can revert this veto effect. Altogether, these findings support the notion that NK cells can recognize self-cells possibly affecting both APC function and interaction between lymphocytes and microenvironment leading to autoreactivity.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages47-57
Number of pages11
Volume1109
DOIs
Publication statusPublished - Aug 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1109
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Autoantigens
Antigen-Presenting Cells
Cytotoxicity
Stromal Cells
Cell Communication
Natural Killer Cells
Histocompatibility Antigens
Lymphocytes
Natural Cytotoxicity Triggering Receptor 3
Natural Cytotoxicity Triggering Receptor 1
Skin
Granzymes
NK Cell Lectin-Like Receptor Subfamily K
Perforin
Molecules
T-cells
Isoantigens
Cell proliferation
Fibroblasts
T-Cell Antigen Receptor

Keywords

  • Antigen-presenting cells
  • Mesenchymal stem cells
  • Natural cytotoxicity receptors
  • Natural killer cells
  • NKG2D
  • Skin fibroblast
  • Stromal cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Poggi, A., Prevosto, C., Zancolli, M., Canevali, P., Musso, A., & Zocchi, M. R. (2007). NKG2D and natural cytotoxicity receptors are involved in natural killer cell interaction with self-antigen presenting cells and stromal cells. In Annals of the New York Academy of Sciences (Vol. 1109, pp. 47-57). (Annals of the New York Academy of Sciences; Vol. 1109). https://doi.org/10.1196/annals.1398.007

NKG2D and natural cytotoxicity receptors are involved in natural killer cell interaction with self-antigen presenting cells and stromal cells. / Poggi, Alessandro; Prevosto, Claudia; Zancolli, Marta; Canevali, Paolo; Musso, Alessandra; Zocchi, Maria Raffaella.

Annals of the New York Academy of Sciences. Vol. 1109 2007. p. 47-57 (Annals of the New York Academy of Sciences; Vol. 1109).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Poggi, A, Prevosto, C, Zancolli, M, Canevali, P, Musso, A & Zocchi, MR 2007, NKG2D and natural cytotoxicity receptors are involved in natural killer cell interaction with self-antigen presenting cells and stromal cells. in Annals of the New York Academy of Sciences. vol. 1109, Annals of the New York Academy of Sciences, vol. 1109, pp. 47-57. https://doi.org/10.1196/annals.1398.007
Poggi A, Prevosto C, Zancolli M, Canevali P, Musso A, Zocchi MR. NKG2D and natural cytotoxicity receptors are involved in natural killer cell interaction with self-antigen presenting cells and stromal cells. In Annals of the New York Academy of Sciences. Vol. 1109. 2007. p. 47-57. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1398.007
Poggi, Alessandro ; Prevosto, Claudia ; Zancolli, Marta ; Canevali, Paolo ; Musso, Alessandra ; Zocchi, Maria Raffaella. / NKG2D and natural cytotoxicity receptors are involved in natural killer cell interaction with self-antigen presenting cells and stromal cells. Annals of the New York Academy of Sciences. Vol. 1109 2007. pp. 47-57 (Annals of the New York Academy of Sciences).
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