Self class I molecules protect normal cells from lysis mediated by autologous natural killer cells

Ermanno Ciccone, Daniela Pende, Massimo Vitale, Luca Nanni, Carolina Di Donato, Cristina Bottino, Luigia Morelli, Oriane Viale, Antonio Amoroso, Alessandro Moretta, Lorenzo Moretta

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

The surface expression of given HLA class I alleles protects target cells from lysis mediated by natural killer (NK) clones specific for these (or related) alleles. We could define two groups of NK clones specifically recognizing either Cw4 and related C alleles ('group 1') or Cw3 and related C alleles ('group 2'), respectively. Monoclonal antibodies (mAb) to class I molecules should interfere with the interaction between NK receptors and class I molecules, thus resulting in lysis of protected target cells. However, none of the numerous available mAb to class I molecules had this effect. Therefore, we attempted to select new mAb on the basis of their ability to induce lysis of Cw4- or Cw3-protected lymphoblastoid cell lines by 'group 1' or 'group 2' NK clones, respectively. From mice immunized with phytohemagglutinin (PHA)-activated lymphocytes expressing either Cw3 or Cw4 alleles, two mAb were selected, the 6A4 (IgG1) and the A6-136 (IgM), on the basis of their ability to induce lysis of protected target cell. Both mAb immunoprecipitated molecules which, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gave two bands of 45 and 12 kDa, typical of the class I heavy chain and β2 microglobulin, respectively. It has been proposed (but not proven), that self major histocompatibility complex class I molecules protect normal cells from autologous NK cell lysis. Thus, we used the 6A4 and A6-136 mAb to assess this possibility directly. Cw4-specific ('group 1') and Cw3-specific ('group 2') NK clones were isolated from donors expressing the corresponding (or related) protective C alleles. None of these clones lysed autologous PHA-induced blasts, used as target cells. However, addition of the F(ab')2 of 6A4 mAb or the A6-136 mAb resulted in lysis of autologous target cells by 'group 1' or 'group 2' NK clones, respectively. These data provide direct evidence that the expression of class I molecules protects normal cells from lysis by autologous NK cells.

Original languageEnglish
Pages (from-to)1003-1006
Number of pages4
JournalEuropean Journal of Immunology
Volume24
Issue number4
Publication statusPublished - Apr 1994

Fingerprint

Natural Killer Cells
Monoclonal Antibodies
Clone Cells
Alleles
Immunoglobulin Isotypes
Phytohemagglutinins
Major Histocompatibility Complex
Sodium Dodecyl Sulfate
Immunoglobulin M
Polyacrylamide Gel Electrophoresis
Immunoglobulin G
Lymphocytes
Cell Line

Keywords

  • Major histocompatibility complex
  • Monoclonal antibodies
  • Natural killer cells

ASJC Scopus subject areas

  • Immunology

Cite this

Self class I molecules protect normal cells from lysis mediated by autologous natural killer cells. / Ciccone, Ermanno; Pende, Daniela; Vitale, Massimo; Nanni, Luca; Di Donato, Carolina; Bottino, Cristina; Morelli, Luigia; Viale, Oriane; Amoroso, Antonio; Moretta, Alessandro; Moretta, Lorenzo.

In: European Journal of Immunology, Vol. 24, No. 4, 04.1994, p. 1003-1006.

Research output: Contribution to journalArticle

Ciccone, E, Pende, D, Vitale, M, Nanni, L, Di Donato, C, Bottino, C, Morelli, L, Viale, O, Amoroso, A, Moretta, A & Moretta, L 1994, 'Self class I molecules protect normal cells from lysis mediated by autologous natural killer cells', European Journal of Immunology, vol. 24, no. 4, pp. 1003-1006.
Ciccone, Ermanno ; Pende, Daniela ; Vitale, Massimo ; Nanni, Luca ; Di Donato, Carolina ; Bottino, Cristina ; Morelli, Luigia ; Viale, Oriane ; Amoroso, Antonio ; Moretta, Alessandro ; Moretta, Lorenzo. / Self class I molecules protect normal cells from lysis mediated by autologous natural killer cells. In: European Journal of Immunology. 1994 ; Vol. 24, No. 4. pp. 1003-1006.
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abstract = "The surface expression of given HLA class I alleles protects target cells from lysis mediated by natural killer (NK) clones specific for these (or related) alleles. We could define two groups of NK clones specifically recognizing either Cw4 and related C alleles ('group 1') or Cw3 and related C alleles ('group 2'), respectively. Monoclonal antibodies (mAb) to class I molecules should interfere with the interaction between NK receptors and class I molecules, thus resulting in lysis of protected target cells. However, none of the numerous available mAb to class I molecules had this effect. Therefore, we attempted to select new mAb on the basis of their ability to induce lysis of Cw4- or Cw3-protected lymphoblastoid cell lines by 'group 1' or 'group 2' NK clones, respectively. From mice immunized with phytohemagglutinin (PHA)-activated lymphocytes expressing either Cw3 or Cw4 alleles, two mAb were selected, the 6A4 (IgG1) and the A6-136 (IgM), on the basis of their ability to induce lysis of protected target cell. Both mAb immunoprecipitated molecules which, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gave two bands of 45 and 12 kDa, typical of the class I heavy chain and β2 microglobulin, respectively. It has been proposed (but not proven), that self major histocompatibility complex class I molecules protect normal cells from autologous NK cell lysis. Thus, we used the 6A4 and A6-136 mAb to assess this possibility directly. Cw4-specific ('group 1') and Cw3-specific ('group 2') NK clones were isolated from donors expressing the corresponding (or related) protective C alleles. None of these clones lysed autologous PHA-induced blasts, used as target cells. However, addition of the F(ab')2 of 6A4 mAb or the A6-136 mAb resulted in lysis of autologous target cells by 'group 1' or 'group 2' NK clones, respectively. These data provide direct evidence that the expression of class I molecules protects normal cells from lysis by autologous NK cells.",
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AU - Ciccone, Ermanno

AU - Pende, Daniela

AU - Vitale, Massimo

AU - Nanni, Luca

AU - Di Donato, Carolina

AU - Bottino, Cristina

AU - Morelli, Luigia

AU - Viale, Oriane

AU - Amoroso, Antonio

AU - Moretta, Alessandro

AU - Moretta, Lorenzo

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N2 - The surface expression of given HLA class I alleles protects target cells from lysis mediated by natural killer (NK) clones specific for these (or related) alleles. We could define two groups of NK clones specifically recognizing either Cw4 and related C alleles ('group 1') or Cw3 and related C alleles ('group 2'), respectively. Monoclonal antibodies (mAb) to class I molecules should interfere with the interaction between NK receptors and class I molecules, thus resulting in lysis of protected target cells. However, none of the numerous available mAb to class I molecules had this effect. Therefore, we attempted to select new mAb on the basis of their ability to induce lysis of Cw4- or Cw3-protected lymphoblastoid cell lines by 'group 1' or 'group 2' NK clones, respectively. From mice immunized with phytohemagglutinin (PHA)-activated lymphocytes expressing either Cw3 or Cw4 alleles, two mAb were selected, the 6A4 (IgG1) and the A6-136 (IgM), on the basis of their ability to induce lysis of protected target cell. Both mAb immunoprecipitated molecules which, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gave two bands of 45 and 12 kDa, typical of the class I heavy chain and β2 microglobulin, respectively. It has been proposed (but not proven), that self major histocompatibility complex class I molecules protect normal cells from autologous NK cell lysis. Thus, we used the 6A4 and A6-136 mAb to assess this possibility directly. Cw4-specific ('group 1') and Cw3-specific ('group 2') NK clones were isolated from donors expressing the corresponding (or related) protective C alleles. None of these clones lysed autologous PHA-induced blasts, used as target cells. However, addition of the F(ab')2 of 6A4 mAb or the A6-136 mAb resulted in lysis of autologous target cells by 'group 1' or 'group 2' NK clones, respectively. These data provide direct evidence that the expression of class I molecules protects normal cells from lysis by autologous NK cells.

AB - The surface expression of given HLA class I alleles protects target cells from lysis mediated by natural killer (NK) clones specific for these (or related) alleles. We could define two groups of NK clones specifically recognizing either Cw4 and related C alleles ('group 1') or Cw3 and related C alleles ('group 2'), respectively. Monoclonal antibodies (mAb) to class I molecules should interfere with the interaction between NK receptors and class I molecules, thus resulting in lysis of protected target cells. However, none of the numerous available mAb to class I molecules had this effect. Therefore, we attempted to select new mAb on the basis of their ability to induce lysis of Cw4- or Cw3-protected lymphoblastoid cell lines by 'group 1' or 'group 2' NK clones, respectively. From mice immunized with phytohemagglutinin (PHA)-activated lymphocytes expressing either Cw3 or Cw4 alleles, two mAb were selected, the 6A4 (IgG1) and the A6-136 (IgM), on the basis of their ability to induce lysis of protected target cell. Both mAb immunoprecipitated molecules which, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gave two bands of 45 and 12 kDa, typical of the class I heavy chain and β2 microglobulin, respectively. It has been proposed (but not proven), that self major histocompatibility complex class I molecules protect normal cells from autologous NK cell lysis. Thus, we used the 6A4 and A6-136 mAb to assess this possibility directly. Cw4-specific ('group 1') and Cw3-specific ('group 2') NK clones were isolated from donors expressing the corresponding (or related) protective C alleles. None of these clones lysed autologous PHA-induced blasts, used as target cells. However, addition of the F(ab')2 of 6A4 mAb or the A6-136 mAb resulted in lysis of autologous target cells by 'group 1' or 'group 2' NK clones, respectively. These data provide direct evidence that the expression of class I molecules protects normal cells from lysis by autologous NK cells.

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