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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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Expression of  mCD1.1 renders RMA/S as resistant to day 5 and 6 A-LAKs as  the classical class I MHC–expressing RMA cell line. 51Cr-labeled  targets were incubated with  pooled day 5 and 6 B6 A-LAKs  for 4 h. Each data point represents  triplicate determinations, and data  are shown as means ± SD. All  spontaneous release values were  <17.9%. This experiment was repeated three times with similar  results.
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Figure 3: Expression of mCD1.1 renders RMA/S as resistant to day 5 and 6 A-LAKs as the classical class I MHC–expressing RMA cell line. 51Cr-labeled targets were incubated with pooled day 5 and 6 B6 A-LAKs for 4 h. Each data point represents triplicate determinations, and data are shown as means ± SD. All spontaneous release values were <17.9%. This experiment was repeated three times with similar results.

Mentions: The A-LAK–mediated cytotoxicity data demonstrated the protective effect of mCD1.1 expression on RMA/S susceptibility to A-LAK lysis. However, it did not show its target protection/A-LAK inhibitory efficiency compared with that of classical class I MHC. To address this issue, the level of RMA/S.CD1.1 lysis by pooled day 5 and 6 B6 A-LAKs was compared with that of RMA (from which the class I MHC–deficient RMA/S is derived). The class I MHC–positive cell line, RMA, is resistant to day 5 and 6 A-LAK lysis (Fig. 3) and A-LAKs selected at several other time points of culture in rIL-2 (data not shown), whereas RMA/S is lysed to a similar degree as the NK cell–sensitive T lymphoma, Yac-1. In contrast, RMA/S.CD1.1 is as resistant to day 5 and 6 A-LAK cytotoxic activity as RMA (Fig. 3). Thus, these results suggest that mCD1.1 can negatively regulate NK cell cytotoxicity to the same extent as classical class I MHC. Since the day 5 and 6 B6 A-LAKs failed to lyse both RMA and RMA/S.CD1.1, this further suggests that these A-LAKs can be negatively regulated by both classical MHC class I molecules and mCD1.1.


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)

Expression of  mCD1.1 renders RMA/S as resistant to day 5 and 6 A-LAKs as  the classical class I MHC–expressing RMA cell line. 51Cr-labeled  targets were incubated with  pooled day 5 and 6 B6 A-LAKs  for 4 h. Each data point represents  triplicate determinations, and data  are shown as means ± SD. All  spontaneous release values were  <17.9%. This experiment was repeated three times with similar  results.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Expression of mCD1.1 renders RMA/S as resistant to day 5 and 6 A-LAKs as the classical class I MHC–expressing RMA cell line. 51Cr-labeled targets were incubated with pooled day 5 and 6 B6 A-LAKs for 4 h. Each data point represents triplicate determinations, and data are shown as means ± SD. All spontaneous release values were <17.9%. This experiment was repeated three times with similar results.
Mentions: The A-LAK–mediated cytotoxicity data demonstrated the protective effect of mCD1.1 expression on RMA/S susceptibility to A-LAK lysis. However, it did not show its target protection/A-LAK inhibitory efficiency compared with that of classical class I MHC. To address this issue, the level of RMA/S.CD1.1 lysis by pooled day 5 and 6 B6 A-LAKs was compared with that of RMA (from which the class I MHC–deficient RMA/S is derived). The class I MHC–positive cell line, RMA, is resistant to day 5 and 6 A-LAK lysis (Fig. 3) and A-LAKs selected at several other time points of culture in rIL-2 (data not shown), whereas RMA/S is lysed to a similar degree as the NK cell–sensitive T lymphoma, Yac-1. In contrast, RMA/S.CD1.1 is as resistant to day 5 and 6 A-LAK cytotoxic activity as RMA (Fig. 3). Thus, these results suggest that mCD1.1 can negatively regulate NK cell cytotoxicity to the same extent as classical class I MHC. Since the day 5 and 6 B6 A-LAKs failed to lyse both RMA and RMA/S.CD1.1, this further suggests that these A-LAKs can be negatively regulated by both classical MHC class I molecules and mCD1.1.

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