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NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor.

Brooks AG, Posch PE, Scorzelli CJ, Borrego F, Coligan JE - J. Exp. Med. (1997)

Bottom Line: CD94 has recently been shown to be a 26-kD protein covalently associated with an unidentified 43-kD protein(s).Cell surface expression of NKG2A is dependent on the association with CD94 as glycosylation patterns characteristic of mature proteins are found only in NKG2A that is associated with CD94.Similar motifs are found on Ly49 and killer cell inhibitory receptors, which also transmit negative signals to NK cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.

ABSTRACT
CD94 is a C-type lectin expressed by natural killer (NK) cells and a subset of T cells. Blocking studies using anti-CD94 mAbs have suggested that it is a receptor for human leukocyte antigen class I molecules. CD94 has recently been shown to be a 26-kD protein covalently associated with an unidentified 43-kD protein(s). This report shows that NKG2A, a 43-kD protein, is covalently associated with CD94 on the surface of NK cells. Cell surface expression of NKG2A is dependent on the association with CD94 as glycosylation patterns characteristic of mature proteins are found only in NKG2A that is associated with CD94. Analysis of NK cell clones showed that NKG2A was expressed in all NK cell clones whose CD16-dependent killing was inhibited by cross-linking CD94. The induction of an inhibitory signal is consistent with the presence of two immunoreceptor tyrosine-based inhibitory motifs (V/LXYXXL) on the cytoplasmic domain of NKG2A. Similar motifs are found on Ly49 and killer cell inhibitory receptors, which also transmit negative signals to NK cells.

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Related in: MedlinePlus

CD94 cross-linking inhibits CD16-mediated lysis of NKG2A  positive NK cell clones. 51Cr-labeled P815 target cells were either preincubated with anti-CD16 (anti-CD16), or anti-CD16 and anti-CD94  (anti-CD16 + anti-CD94) or complete medium (untreated) prior to incubation with the NKG2A positive NK cell clones AR8 and JS22 or the  NKG2A negative NK cell clone, AR19 for 4 h. 51Cr released was measured in a γ counter and the percentage of specific lysis calculated.
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Figure 4: CD94 cross-linking inhibits CD16-mediated lysis of NKG2A positive NK cell clones. 51Cr-labeled P815 target cells were either preincubated with anti-CD16 (anti-CD16), or anti-CD16 and anti-CD94 (anti-CD16 + anti-CD94) or complete medium (untreated) prior to incubation with the NKG2A positive NK cell clones AR8 and JS22 or the NKG2A negative NK cell clone, AR19 for 4 h. 51Cr released was measured in a γ counter and the percentage of specific lysis calculated.

Mentions: Data from three NK cell clones are shown in Fig. 4. Low levels of lysis of P815 target cells by both the NKG2A positive clones AR8 and JS22, and the NKG2A negative clone AR19 were observed in the absence of any mAb (Fig. 4). As expected, preincubation of P815 cells with anti-CD16 lead to a significant increase in target cell lysis by all clones. The presence of anti-CD94 had little effect on CD16dependent lysis of P815 cells by AR19. However crosslinking of CD94 on the NKG2A positive clones, AR8 and JS22, markedly inhibited anti-CD16-mediated lysis of P815 cells to levels comparable with the untreated controls. Our data suggest that NKG2A expression is required for the generation of an inhibitory signal after CD94 cross-linking. However, whether all NK cell clones expressing NKG2A are inhibited after CD94 cross-linking awaits a more extensive clonal analysis and is the subject of ongoing research.


NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor.

Brooks AG, Posch PE, Scorzelli CJ, Borrego F, Coligan JE - J. Exp. Med. (1997)

CD94 cross-linking inhibits CD16-mediated lysis of NKG2A  positive NK cell clones. 51Cr-labeled P815 target cells were either preincubated with anti-CD16 (anti-CD16), or anti-CD16 and anti-CD94  (anti-CD16 + anti-CD94) or complete medium (untreated) prior to incubation with the NKG2A positive NK cell clones AR8 and JS22 or the  NKG2A negative NK cell clone, AR19 for 4 h. 51Cr released was measured in a γ counter and the percentage of specific lysis calculated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196137&req=5

Figure 4: CD94 cross-linking inhibits CD16-mediated lysis of NKG2A positive NK cell clones. 51Cr-labeled P815 target cells were either preincubated with anti-CD16 (anti-CD16), or anti-CD16 and anti-CD94 (anti-CD16 + anti-CD94) or complete medium (untreated) prior to incubation with the NKG2A positive NK cell clones AR8 and JS22 or the NKG2A negative NK cell clone, AR19 for 4 h. 51Cr released was measured in a γ counter and the percentage of specific lysis calculated.
Mentions: Data from three NK cell clones are shown in Fig. 4. Low levels of lysis of P815 target cells by both the NKG2A positive clones AR8 and JS22, and the NKG2A negative clone AR19 were observed in the absence of any mAb (Fig. 4). As expected, preincubation of P815 cells with anti-CD16 lead to a significant increase in target cell lysis by all clones. The presence of anti-CD94 had little effect on CD16dependent lysis of P815 cells by AR19. However crosslinking of CD94 on the NKG2A positive clones, AR8 and JS22, markedly inhibited anti-CD16-mediated lysis of P815 cells to levels comparable with the untreated controls. Our data suggest that NKG2A expression is required for the generation of an inhibitory signal after CD94 cross-linking. However, whether all NK cell clones expressing NKG2A are inhibited after CD94 cross-linking awaits a more extensive clonal analysis and is the subject of ongoing research.

Bottom Line: CD94 has recently been shown to be a 26-kD protein covalently associated with an unidentified 43-kD protein(s).Cell surface expression of NKG2A is dependent on the association with CD94 as glycosylation patterns characteristic of mature proteins are found only in NKG2A that is associated with CD94.Similar motifs are found on Ly49 and killer cell inhibitory receptors, which also transmit negative signals to NK cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.

ABSTRACT
CD94 is a C-type lectin expressed by natural killer (NK) cells and a subset of T cells. Blocking studies using anti-CD94 mAbs have suggested that it is a receptor for human leukocyte antigen class I molecules. CD94 has recently been shown to be a 26-kD protein covalently associated with an unidentified 43-kD protein(s). This report shows that NKG2A, a 43-kD protein, is covalently associated with CD94 on the surface of NK cells. Cell surface expression of NKG2A is dependent on the association with CD94 as glycosylation patterns characteristic of mature proteins are found only in NKG2A that is associated with CD94. Analysis of NK cell clones showed that NKG2A was expressed in all NK cell clones whose CD16-dependent killing was inhibited by cross-linking CD94. The induction of an inhibitory signal is consistent with the presence of two immunoreceptor tyrosine-based inhibitory motifs (V/LXYXXL) on the cytoplasmic domain of NKG2A. Similar motifs are found on Ly49 and killer cell inhibitory receptors, which also transmit negative signals to NK cells.

Show MeSH
Related in: MedlinePlus