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The murine nonclassical class I major histocompatibility complex-like CD1.1 molecule protects target cells from lymphokine-activated killer cell cytolysis.

Chang CS, Brossay L, Kronenberg M, Kane KP - J. Exp. Med. (1999)

Bottom Line: Passage of effector cells in recombinant interleukin (rIL)-2 enhanced protection by mCD1.1, suggesting an expansion of relevant A-LAK population(s) or modulation of A-LAK receptor expression.CD1.1 is by far the most divergent class I molecule capable of regulating NK cell activity.Finally, mCD1.1 expression rendered RMA/S cells resistant to lysis by A-LAK of multiple mouse strains.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.

ABSTRACT
Classical class I major histocompatibility complex (MHC) molecules, as well as the nonclassical class I histocompatibility leukocyte antigen (HLA)-E molecule, can negatively regulate natural killer (NK) cell cytotoxicity through engagement of NK inhibitory receptors. We show that expression of murine (m)CD1.1, a nonpolymorphic nonclassical MHC class I-like molecule encoded outside the MHC, protects NK-sensitive RMA/S target cells from adherent lymphokine-activated killer cell (A-LAK) cytotoxicity. Passage of effector cells in recombinant interleukin (rIL)-2 enhanced protection by mCD1.1, suggesting an expansion of relevant A-LAK population(s) or modulation of A-LAK receptor expression. Murine CD1. 1 conferred protection from lysis by rIL-2-activated spleen cells of recombination activating gene (Rag)-1(-/-) mice, which lack B and T cells, demonstrating that mCD1.1 can protect RMA/S cells from lysis by NK cells. An antibody specific for mCD1.1 partially restored A-LAK lysis of RMA/S.CD1.1 transfectants, indicating that cell surface mCD1.1 can confer protection from lysis; therefore, mCD1.1 possibly acts through interaction with an NK inhibitory receptor. CD1.1 is by far the most divergent class I molecule capable of regulating NK cell activity. Finally, mCD1.1 expression rendered RMA/S cells resistant to lysis by A-LAK of multiple mouse strains. The conserved structure of mCD1.1 and pattern of mCD1.1 resistance from A-LAK lysis suggest that mCD1.1 may be a ligand for a conserved NK inhibitory receptor.

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The mCD1.1 transfectant of RMA/S is not intrinsically resistant to cell-mediated  lysis. RMA/S and RMA/S.  CD1.1 cells were grown overnight at 26°C, then 51Cr-labeled  and pulsed with or without 400  μg/ml of NP peptide at 37°C for  1 h. The cells were then incubated with CTL clone 3/4 for 4 h  at various E/T ratios in triplicate.  Results are shown as means ±  SD. In all cases, the spontaneous  release values were <9.4%.  Identical results were obtained in  two additional experiments.
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Figure 4: The mCD1.1 transfectant of RMA/S is not intrinsically resistant to cell-mediated lysis. RMA/S and RMA/S. CD1.1 cells were grown overnight at 26°C, then 51Cr-labeled and pulsed with or without 400 μg/ml of NP peptide at 37°C for 1 h. The cells were then incubated with CTL clone 3/4 for 4 h at various E/T ratios in triplicate. Results are shown as means ± SD. In all cases, the spontaneous release values were <9.4%. Identical results were obtained in two additional experiments.

Mentions: It might be argued that upon mCD1.1 transfection, RMA/S simply becomes resistant to cell-mediated cytotoxicity, independent of killer cell recognition events. However, this interpretation is not supported by the observation that both RMA/S and RMA/S.CD1.1 were lysed efficiently by A-LAKs generated from early time points (Fig. 2). In addition, after induction of higher classical class I MHC expression at 26°C and incubation with peptide antigen, both RMA/S and the RMA/S.CD1.1 transfectant were lysed to a similarly high level by the influenza NP– specific, Db-restricted CTL clone 3/4 (Fig. 4). For instance, only after pulsing with Db-specific influenza NP peptide, but not in the absence of peptide or in the presence of the Kb-binding OVA peptide, SIINFEKL (data not shown), can lysis be detected. This indicated that intracellular apoptotic pathways remain intact upon mCD1.1 transfection. Thus, RMA/S.CD1.1 is not intrinsically resistant to cell-mediated lysis.


The murine nonclassical class I major histocompatibility complex-like CD1.1 molecule protects target cells from lymphokine-activated killer cell cytolysis.

Chang CS, Brossay L, Kronenberg M, Kane KP - J. Exp. Med. (1999)

The mCD1.1 transfectant of RMA/S is not intrinsically resistant to cell-mediated  lysis. RMA/S and RMA/S.  CD1.1 cells were grown overnight at 26°C, then 51Cr-labeled  and pulsed with or without 400  μg/ml of NP peptide at 37°C for  1 h. The cells were then incubated with CTL clone 3/4 for 4 h  at various E/T ratios in triplicate.  Results are shown as means ±  SD. In all cases, the spontaneous  release values were <9.4%.  Identical results were obtained in  two additional experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192909&req=5

Figure 4: The mCD1.1 transfectant of RMA/S is not intrinsically resistant to cell-mediated lysis. RMA/S and RMA/S. CD1.1 cells were grown overnight at 26°C, then 51Cr-labeled and pulsed with or without 400 μg/ml of NP peptide at 37°C for 1 h. The cells were then incubated with CTL clone 3/4 for 4 h at various E/T ratios in triplicate. Results are shown as means ± SD. In all cases, the spontaneous release values were <9.4%. Identical results were obtained in two additional experiments.
Mentions: It might be argued that upon mCD1.1 transfection, RMA/S simply becomes resistant to cell-mediated cytotoxicity, independent of killer cell recognition events. However, this interpretation is not supported by the observation that both RMA/S and RMA/S.CD1.1 were lysed efficiently by A-LAKs generated from early time points (Fig. 2). In addition, after induction of higher classical class I MHC expression at 26°C and incubation with peptide antigen, both RMA/S and the RMA/S.CD1.1 transfectant were lysed to a similarly high level by the influenza NP– specific, Db-restricted CTL clone 3/4 (Fig. 4). For instance, only after pulsing with Db-specific influenza NP peptide, but not in the absence of peptide or in the presence of the Kb-binding OVA peptide, SIINFEKL (data not shown), can lysis be detected. This indicated that intracellular apoptotic pathways remain intact upon mCD1.1 transfection. Thus, RMA/S.CD1.1 is not intrinsically resistant to cell-mediated lysis.

Bottom Line: Passage of effector cells in recombinant interleukin (rIL)-2 enhanced protection by mCD1.1, suggesting an expansion of relevant A-LAK population(s) or modulation of A-LAK receptor expression.CD1.1 is by far the most divergent class I molecule capable of regulating NK cell activity.Finally, mCD1.1 expression rendered RMA/S cells resistant to lysis by A-LAK of multiple mouse strains.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.

ABSTRACT
Classical class I major histocompatibility complex (MHC) molecules, as well as the nonclassical class I histocompatibility leukocyte antigen (HLA)-E molecule, can negatively regulate natural killer (NK) cell cytotoxicity through engagement of NK inhibitory receptors. We show that expression of murine (m)CD1.1, a nonpolymorphic nonclassical MHC class I-like molecule encoded outside the MHC, protects NK-sensitive RMA/S target cells from adherent lymphokine-activated killer cell (A-LAK) cytotoxicity. Passage of effector cells in recombinant interleukin (rIL)-2 enhanced protection by mCD1.1, suggesting an expansion of relevant A-LAK population(s) or modulation of A-LAK receptor expression. Murine CD1. 1 conferred protection from lysis by rIL-2-activated spleen cells of recombination activating gene (Rag)-1(-/-) mice, which lack B and T cells, demonstrating that mCD1.1 can protect RMA/S cells from lysis by NK cells. An antibody specific for mCD1.1 partially restored A-LAK lysis of RMA/S.CD1.1 transfectants, indicating that cell surface mCD1.1 can confer protection from lysis; therefore, mCD1.1 possibly acts through interaction with an NK inhibitory receptor. CD1.1 is by far the most divergent class I molecule capable of regulating NK cell activity. Finally, mCD1.1 expression rendered RMA/S cells resistant to lysis by A-LAK of multiple mouse strains. The conserved structure of mCD1.1 and pattern of mCD1.1 resistance from A-LAK lysis suggest that mCD1.1 may be a ligand for a conserved NK inhibitory receptor.

Show MeSH
Related in: MedlinePlus