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The Journal of Immunology, 2005, 175: 7796-7799.
Copyright © 2005 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Lectin-Like Transcript-1 Is a Ligand for the Inhibitory Human NKR-P1A Receptor1

David B. Rosen*, Jayaram Bettadapura{dagger}, Mohammed Alsharifi{dagger}, Porunelloor A. Mathew{ddagger}, Hilary S. Warren2,{dagger} and Lewis L. Lanier2,3,*

* Department of Microbiology and Immunology, The Cancer Research Institute, and Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143; {dagger} Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University, Canberra City, Australian Capital Territory, Australia; and {ddagger} Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results and Discussion
 Disclosures
 References
 
Increasingly, roles are emerging for C-type lectin receptors in immune regulation. One receptor whose function has remained largely enigmatic is human NKR-P1A (CD161), present on NK cells and subsets of T cells. In this study, we demonstrate that the lectin-like transcript-1 (LLT1) is a physiologic ligand for NKR-P1A. LLT1-containing liposomes bind to NKR-P1A+ cells, and binding is inhibited by anti-NKR-P1A mAb. Additionally, LLT1 activates NFAT-GFP reporter cells expressing a CD3{zeta}-NKR-P1A chimeric receptor; reciprocally, reporter cells with a CD3{zeta}-LLT1 chimeric receptor are stimulated by NKR-P1A. Moreover, LLT1 on target cells can inhibit NK cytotoxicity via interactions with NKR-P1A.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results and Discussion
 Disclosures
 References
 
Rodents have several Klrb1 (also named Nkrp1) genes encoding either activating or inhibitory NK receptors of the C-type lectin superfamily, including Nkr-p1c, the NK1.1 Ag defining mouse NK cells (1). By contrast, only a single, nonpolymorphic gene in the Nkrp1 family, KLRB1, exists in humans (2). KLRB1 encodes a type II disulfide-linked homodimer, named CD161 or NKR-P1A, which is expressed on most NK cells. Human NKR-P1A is on a subset of peripheral T cells, including CD4+ and CD8+ T cells (mostly effector/memory phenotype), invariant NKT cells, and {gamma}{delta}-TCR+ T cells, and on a subset of CD3+ thymocytes (2).

NKR-P1A is expressed on immature human NK cells, before acquisition of CD16 or CD56 (3), and its expression is up-regulated on mature NK cells by IL-12 (4, 5). NKR-P1A on CD4+ T cells and {gamma}{delta}-TCR+ T cells has been implicated in transendothelial migration (6, 7). Additionally, anti-NKR-P1A mAbs costimulate the anti-CD3 mAb-induced proliferation of CD1d-specific NK T cells (8) and induce proliferation of immature thymocytes (9). Cross-linking with an anti-NKR-P1A mAb inhibits human NK cell-mediated cytotoxicity against FcR+ target cells (4, 5).

Recently, ligands for two mouse Klrb1 family members have been identified (10, 11). The activating Nkr-p1f receptor recognizes Clr-g (encoded by Clec2i) (10), and the inhibitory Nkr-p1d recognizes Clr-b (encoded by Clec2d) (11). Another name for Clr-b is osteoclast inhibitory lectin, because it was also identified as an osteoblast-derived glycoprotein, which inhibits in vitro osteoclastogenesis (12, 13). Although mice have multiple Clr family genes, only one ortholog, CLEC2D (also named lectin-like transcript-1 (LLT1)4), exists in humans. Like mouse Clr-b, human LLT1 blocks osteoclast differentiation (12, 13). Mouse and human Clec2 gene products are type II proteins of the C-type lectin superfamily.

The ability of mouse Nkrp1 family receptors to recognize Clr ligands prompted the question of whether this interaction is conserved in humans. In this study, we have examined whether LLT1 serves as a ligand of human NKR-P1A and have described the functional consequences of this novel receptor-ligand interaction.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results and Discussion
 Disclosures
 References
 
LLT1 liposomes

A cDNA encoding the extracellular domain of LLT1 with a N-terminal 6-His tag was cloned into a pFASTBac vector, modified to encode a signal sequence for ecdysteroid UDP glucosyltransferase, and expressed in the Bac-to-Bac system (Invitrogen). Recombinant protein was purified by Ni-NTA affinity chromatography. The preparation of LLT1-fluorescent liposome complexes and the procedure for binding to cells was described previously (14, 15, 16). To ensure binding was specific, cells were incubated with an anti-CD161 mAb or an isotype-matched control Ig (10 µg/ml) before incubating with the liposome-rLLT1 complexes.

Reporter cell assays

An NFAT-GFP reporter construct was stably transduced into 2B4 T cell hybridoma cells (provided by H. Arase, Osaka University, Osaka, Japan). NFAT-GFP reporter cells were transduced with CD3{zeta}-LLT1 or CD3{zeta}-NKR-P1A chimeric receptors and analyzed as described (17, 18). Briefly, reporter and stimulator cells were cocultured at a 1:4 ratio for 16 h and then analyzed for GFP expression by flow cytometry.

Constructs and transductions

cDNAs for human NKp80 (provided by J. P. Houchins, R&D Systems, Minneapolis, MN), human CD69, LLT1 with a C-terminal Flag-epitope, human NKR-P1A, and the reporter constructs were subcloned into pMXs-puro vectors (provided by T. Kitamura, University of Tokyo, Tokyo, Japan) (19). Chimeric receptors were generated by fusing the extracellular and transmembrane domains of either LLT1 or NKR-P1A to the intracellular domain of human CD3{zeta}. Plasmid constructs were transfected into Phoenix packaging cells (20) to produce retroviruses (18, 21). Infected cells were selected in medium containing 1 µg/ml puromycin.

Antibodies

Mouse anti-human NKR-P1A mAbs DX1 and DX12 were produced in our laboratory, and HP3G10 was purchased from MBL International.

Primary cell cultures and cytotoxicity assays

Venous blood was obtained from healthy volunteers, under procedures approved by the Human Ethics Committees of the Australian Capital Territory Department of Health and Community Care and the Australian National University (Canberra, Australia) and the University of California, San Francisco, Committee on Human Research. Polyclonal NK cells were generated and tested in cytotoxicity assays as described previously (22, 23, 24).


   Results and Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
Disclosures
 References
 
LLT1 liposomes bind human NKR-P1A

We generated fluorescent-labeled liposomes containing human LLT1 and evaluated their staining of the mouse Ba/F3 pro-B cell line and BaF/3 cells stably transduced with human NKR-P1A (BaF/3-NKR-P1A). LLT1-liposome complexes bound specifically to BaF/3-NKR-P1A, but not parental BaF/3 (Fig. 1A). This interaction was specifically blocked by anti-NKR-P1A mAb (dashed line), but not control Ig (solid). LLT1-liposomes also bound to the human NK cell line YT transfected with NKR-P1A (YT-NKR-P1A), but not to untransfected YT cells (Fig. 1B), and the interaction was prevented by all anti-NKR-P1A mAbs tested (i.e., DX1, DX12, HP3G10), but not by control Ig (Fig. 1B). Furthermore, LLT1-liposomes recognized endogenous NKR-P1A expressed by in vitro-activated human peripheral blood NK cells, and the binding was inhibited by anti-NKR-P1A mAbs, but not by control Ig (Fig. 1C).



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  		FIGURE 1. Binding of LLT1 liposomes to NKR-P1A+ cells. A, Left, Amounts of NKR-P1A on untransfected BaF/3 and NKR-P1A-transfected BaF/3 cells (solid, anti-NKR-P1A; shaded, control). Right, LLT1 liposomes stain BaF/3-NKR-P1A in the presence of isotype-matched control mAb (solid line), but not in the presence of anti-NKR-P1A (dashed) (10 µg/ml), and do not stain untransfected BaF/3. B, Left, Amounts of NKR-P1A on untransfected YT and NKR-P1A-transfected YT cells (solid line, anti-NKR-P1A; shaded, isotype-matched control Ig). Right, LLT1 liposomes (solid) stained YT-NKR-P1A but not YT (shaded, unstained cells). Bottom, LLT1 liposome binding to YT-NKR-P1A (solid line) in the presence of control Ig or blocking anti-NKR-P1A mAbs (dashed). C, Left, NKR-P1A staining of in vitro-cultured peripheral blood NK cells (solid, anti-NKR-P1A; shaded, isotype-matched control Ig). Right, LLT1 liposome binding to in vitro-cultured NK cells alone (solid) or in the presence of control Ig or blocking anti-NKR-P1A mAbs (dashed).

 
LLT1 reporter cells recognize NKR-P1A

We created mouse 2B4 NFAT-GFP reporter cells (18) expressing a chimeric protein consisting of the extracellular and transmembrane domains of LLT1 and the intracellular domain of CD3{zeta}. Receptor engagement of the CD3{zeta}-LLT1 chimera resulted in signaling from the CD3{zeta} ITAMs, activation of NFAT, and the expression of GFP. Coculture of the LLT1 reporter cells with BaF/3-NKR-P1A cells resulted in robust NFAT-GFP activation, whereas coculture with parent BaF/3 or BaF/3-NKp80 cells did not (Fig. 2A). Moreover, the activation of CD3{zeta}-LLT1 reporter cells by BaF/3-NKR-P1A was specifically blocked by anti-NKR-P1A mAb, but not by control Ig (Fig. 2B).



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  		FIGURE 2. LLT1 and NKR-P1A reporter cells recognize NKR-P1A and LLT1, respectively. A, NKR-P1A-transfected BaF/3, but not parent BaF/3 or BaF/3 expressing human NKp80, induced NFAT (as read out by GFP) when cocultured with the CD3{zeta}-LLT1 chimera NFAT-GFP reporter cells. B, Activation of CD3{zeta}-LLT1 chimera reporter cells by BaF/3-NKR-P1A was blocked by anti-NKR-P1A. C, BaF/3-LLT1, but not parental BaF/3 or BaF/3 expressing human CD69, induced NFAT when cocultured with CD3{zeta}-NKR-P1A chimera NFAT-GFP reporter cells. D, Activation of CD3{zeta}-NKR-P1A chimera reporter cells by BaF/3-LLT1 was blocked by anti-NKR-P1A (10 µg/ml). Maximal stimulation in these reporter cell assays, even by cross-linking the chimeric receptor with mAb, typically results at most in ~60% GFP+ cells (18 ).

 
Similarly, we created reporter cells expressing a CD3{zeta}-NKR-P1A chimera and tested the ability of these cells to recognize LLT1-bearing cells. NKR-P1A reporter cells expressed GFP when cocultured with LLT1-transduced BaF/3 (BaF/3-LLT1), but not with untransfected BaF/3 or BaF/3 expressing human CD69 (BaF/3-CD69) (Fig. 2C). LLT1-induced activation of the NKR-P1A reporter cells was inhibited by anti-NKR-P1A mAbs, but not control Ig (Fig. 2D).

LLT1 inhibits NK cytotoxicity via NKR-P1A

Prior studies have shown that anti-NKR-P1A mAb inhibits NK cell-mediated lysis of FcR-bearing cells (2). Now with a defined ligand for NKR-P1A, we examined the function of NKR-P1A in NK cells using target cells expressing its physiological ligand. EBV-transformed 721.221 B lymphoblastoid cells express LLT1 mRNA, as detected by PCR (not shown). In accordance, we found that 721.221 activated CD3{zeta}-NKR-P1A reporter cells, an effect that was blocked by anti-NKR-P1A, but not control Ig (Fig. 3A).



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  		FIGURE 3. LLT1 inhibits NK cell-mediated cytotoxicity via NKR-P1A. A, 721.221 cells activated NKR-P1A-CD3{zeta} chimera reporter cells, which was blocked by anti-NKR-P1A. B, YT-NKR-P1A cells have diminished cytotoxic capacity against 721.221 targets compared with untransfected YT cells. C, NKR-P1A-mediated inhibition of 721.221 lysis was reversed by anti-NKR-P1A F(ab')2, but not isotype-matched control F(ab')2 (10 µg/ml). D, In vitro-cultured peripheral blood NK cell-mediated cytotoxicity against BaF/3-CD48 was reduced by LLT1 expression (left). LLT1-induced inhibition of NK cell-mediated cytotoxicity against Ba/F3-MICA was reversed by anti-NKR-P1A F(ab')2 but not isotype-matched control F(ab')2 (right).

 
We tested the cytolytic ability of YT and YT-NKR-P1A against 721.221 targets. YT-NKR-P1A cells had diminished cytotoxic capacity against 721.221 compared with untransfected YT (Fig. 3B); equivalent killing by YT and YT-NKR-P1A was seen against CD48-transduced BaF/3 targets, indicating that both YT and YT-NKR-P1A have similar lytic potential (not shown). Furthermore, the NKR-P1A-mediated inhibition of 721.221 lysis by YT-NKR-P1A cells was reversed by anti-NKR-P1A F(ab')2, but not control F(ab')2 (Fig. 3C).

NK cells can be stimulated through several activating receptors that use biochemically distinct signaling pathways, for example, human NKG2D, which recognizes MHC class I chain-related A (MICA), and human CD244, which recognizes CD48 (25). We examined the effects of NKR-P1A on these activation pathways by transducing LLT1 into BaF/3 target cells expressing MICA or CD48 and determining the effect of NKR-P1A engagement on NK cell-mediated cytotoxicity. LLT1 expression by these targets diminished NK cell-mediated cytotoxicity induced by either the CD48/CD244 pathway (Fig. 3D, left) or the MICA/NKG2D pathway (Fig. 3D, right), an effect which was mediated through interactions with NKR-P1A and was reversed by anti-NKR-P1A F(ab')2, but not control F(ab')2 (Fig. 3D).

These data prove that LLT1 is the ligand for human NKR-P1A, and this interaction inhibits NK cytotoxicity. In mice, the LLT1 ortholog Clr-b, like MHC class I, is widely expressed (11). Recently, potential orthologs for NKR-P1A and LLT1, B-NK and B-lec, respectively, have been described in the chicken MHC region (26). This raises the questions of whether B-NK and B-lec interact, and whether NKR-P1A-LLT1-like interactions have been preserved through evolution. LLT1 is transcribed in T cells, B cells, and NK cells (27) and in osteoblast cell lines (13).

Collectively, our findings provide another example of a functional interaction between two genomically linked C-type lectin proteins encoded by genes in the "NK complex." This raises the question of whether other C-type lectins within this genomic region are interacting, and what the functional consequences may be. Additionally, the existence of the LLT1-NKR-P1A interaction in humans provides yet-another mechanism for the fine-tuning of NK cell and T cell responses using an inhibitory receptor that recognizes a non-MHC ligand.


   Acknowledgments
 
We thank Joseph Altin for providing liposomes, Mark Hulett for advice on the Bac-to-Bac system, and Margaret Hilton, Taian Chen, and Allen Sun for technical assistance.


   Disclosures
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
 Disclosures
References
 
The authors have no financial conflict of interest.


   Footnotes
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by National Institutes of Health Grant AI068129 and National Health and Medical Research Council Project Grant 151304. H.S.W. is a Senior Research Fellow of the National Health and Medical Research Council of Australia, and a Visiting Fellow of the Australian National University Medical School and The Canberra Hospital. L.L.L. is an American Cancer Society Research Professor. D.B.R. is supported by a Genentech Graduate Student Fellowship. Back

2 H.S.W. and L.L.L. contributed equally to this work. Back

3 Address correspondence and reprint requests to Dr. Lewis L. Lanier, Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, Box 0414, San Francisco, CA 94143-0414. E-mail address: lewis.lanier{at}ucsf.edu Back

4 Abbreviations used in this paper: LLT1, lectin-like transcript-1; MICA, MHC class I chain-related A. Back

Received for publication September 27, 2005. Accepted for publication October 28, 2005.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
 Disclosures
 References
 

  1. Plougastel, B., C. Dubbelde, W. M. Yokoyama. 2001. Cloning of Clr, a new family of lectin-like genes localized between mouse Nkrp1a and Cd69. Immunogenetics 53: 209-214. [Medline]
  2. Lanier, L. L., C. Chang, J. H. Phillips. 1994. Human NKR-P1A: a disulfide linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J. Immunol. 153: 2417-2428. [Abstract]
  3. Bennett, I. M., O. Zatsepina, L. Zamai, L. Azzoni, T. Mikheeva, B. Perussia. 1996. Definition of a natural killer NKR-P1A+/CD56–/CD16– functionally immature human NK cell subset that differentiates in vitro in the presence of interleukin 12. J. Exp. Med. 184: 1845-1856. [Abstract/Free Full Text]
  4. Azzoni, L., O. Zatsepina, B. Abebe, I. M. Bennett, P. Kanakaraj, B. Perussia. 1998. Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T cells. J. Immunol. 161: 3493-3500. [Abstract/Free Full Text]
  5. Poggi, A., P. Costa, E. Tomasello, L. Moretta. 1998. IL-12-induced up-regulation of NKRP1A expression in human NK cells and consequent NKRP1A-mediated down-regulation of NK cell activation. Eur. J. Immunol. 28: 1611-1616. [Medline]
  6. Poggi, A., P. Costa, M. R. Zocchi, L. Moretta. 1997. NKRP1A molecule is involved in transendothelial migration of CD4+ human T lymphocytes. Immunol. Lett. 57: 121-123. [Medline]
  7. Poggi, A., M. R. Zocchi, P. Costa, E. Ferrero, G. Borsellino, R. Placido, S. Galgani, M. Salvetti, C. Gasperini, G. Ristori, et al 1999. IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of V{delta}2+ TCR {gamma}{delta}+ T lymphocytes from healthy donors and multiple sclerosis patients. J. Immunol. 162: 4349-4354. [Abstract/Free Full Text]
  8. Exley, M., S. Porcelli, M. Furman, J. Garcia, S. Balk. 1998. CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V{alpha}24J{alpha}Q T cell receptor {alpha} chains. J. Exp. Med. 188: 867-876. [Abstract/Free Full Text]
  9. Poggi, A., P. Costa, L. Morelli, C. Cantoni, N. Pella, F. Spada, R. Biassoni, L. Nanni, V. Revello, E. Tomasello, et al 1996. Expression of human NKRP1A by CD34+ immature thymocytes: NKRP1A-mediated regulation of proliferation and cytolytic activity. Eur. J. Immunol. 26: 1266-1272. [Medline]
  10. Iizuka, K., O. V. Naidenko, B. F. Plougastel, D. H. Fremont, W. M. Yokoyama. 2003. Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors. Nat. Immunol. 4: 801-807. [Medline]
  11. Carlyle, J. R., A. M. Jamieson, S. Gasser, C. S. Clingan, H. Arase, D. H. Raulet. 2004. Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors. Proc. Natl. Acad. Sci. USA 101: 3527-3532. [Abstract/Free Full Text]
  12. Zhou, H., V. Kartsogiannis, Y. S. Hu, J. Elliott, J. M. Quinn, W. J. McKinstry, M. T. Gillespie, K. W. Ng. 2001. A novel osteoblast-derived C-type lectin that inhibits osteoclast formation. J. Biol. Chem. 276: 14916-14923. [Abstract/Free Full Text]
  13. Hu, Y. S., H. Zhou, D. Myers, J. M. Quinn, G. J. Atkins, C. Ly, C. Gange, V. Kartsogiannis, J. Elliott, P. Kostakis, et al 2004. Isolation of a human homolog of osteoclast inhibitory lectin that inhibits the formation and function of osteoclasts. J. Bone Miner. Res. 19: 89-99. [Medline]
  14. Warren, H. S., A. L. Jones, C. Freeman, J. Bettadapura, C. R. Parish. 2005. Evidence that the cellular ligand for the human NK cell activation receptor NKp30 is not a heparan sulfate glycosaminoglycan. J. Immunol. 175: 207-212. [Abstract/Free Full Text]
  15. van Broekhoven, C. L., C. R. Parish, C. Demangel, W. J. Britton, J. G. Altin. 2004. Targeting dendritic cells with antigen-containing liposomes: a highly effective procedure for induction of antitumor immunity and for tumor immunotherapy. Cancer Res. 64: 4357-4365. [Abstract/Free Full Text]
  16. Van Broekhoven, C. L., J. G. Altin. 2001. A novel system for convenient detection of low-affinity receptor-ligand interactions: chelator-lipid liposomes engrafted with recombinant CD4 bind to cells expressing MHC class II. Immunol. Cell Biol. 79: 274-284. [Medline]
  17. Arase, H., E. S. Mocarski, A. E. Campbell, A. B. Hill, L. L. Lanier. 2002. Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296: 1323-1326. [Abstract/Free Full Text]
  18. Voehringer, D., D. B. Rosen, L. L. Lanier, R. M. Locksley. 2004. CD200 receptor family members represent novel DAP12-associated activating receptors on basophils and mast cells. J. Biol. Chem. 279: 54117-54123. [Abstract/Free Full Text]
  19. Kitamura, T., Y. Koshino, F. Shibata, T. Oki, H. Nakajima, T. Nosaka, H. Kumagai. 2003. Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. Exp. Hematol. 31: 1007-1014. [Medline]
  20. Kinsella, T. M., G. P. Nolan. 1996. Episomal vectors rapidly and stably produce high-titer recombinant retrovirus. Hum. Gene Ther. 7: 1405-1413. [Medline]
  21. Rosen, D. B., M. Araki, J. A. Hamerman, T. Chen, T. Yamamura, L. L. Lanier. 2004. A structural basis for the association of DAP12 with mouse, but not human, NKG2D. J. Immunol. 173: 2470-2478. [Abstract/Free Full Text]
  22. Lanier, L. L., J. J. Ruitenberg, J. H. Phillips. 1988. Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes. J. Immunol. 141: 3478-3485. [Abstract]
  23. Warren, H. S., P. M. Rana. 2003. An economical adaptation of the RosetteSep procedure for NK cell enrichment from whole blood, and its use with liquid nitrogen stored peripheral blood mononuclear cells. J. Immunol. Methods 280: 135-138. [Medline]
  24. Imai, C., S. Iwamoto, D. Campana. 2005. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood 106: 376-383. [Abstract/Free Full Text]
  25. Lanier, L. L.. 2005. NK cell recognition. Annu. Rev. Immunol. 23: 225-274. [Medline]
  26. Rogers, S. L., T. W. Gobel, B. C. Viertlboeck, S. Milne, S. Beck, J. Kaufman. 2005. Characterization of the chicken C-type lectin-like receptors B-NK and B-lec suggests that the NK complex and the MHC share a common ancestral region. J. Immunol. 174: 3475-3483. [Abstract/Free Full Text]
  27. Boles, K. S., R. Barten, P. R. Kumaresan, J. Trowsdale, P. A. Mathew. 1999. Cloning of a new lectin-like receptor expressed on human NK cells. Immunogenetics 50: 1-7. [Medline]



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W. M. Ballan, B.-A. N. Vu, B. R. Long, C. P. Loo, J. Michaelsson, J. D. Barbour, L. L. Lanier, A. A. Wiznia, J. Abadi, G. J. Fennelly, et al.
Natural Killer Cells in Perinatally HIV-1-Infected Children Exhibit Less Degranulation Compared to HIV-1-Exposed Uninfected Children and Their Expression of KIR2DL3, NKG2C, and NKp46 Correlates with Disease Severity
J. Immunol., September 1, 2007; 179(5): 3362 - 3370.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Ravet, D. Scott-Algara, E. Bonnet, H. K. Tran, T. Tran, N. Nguyen, L. X. Truong, I. Theodorou, F. Barre-Sinoussi, G. Pancino, et al.
Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals
Blood, May 15, 2007; 109(10): 4296 - 4305.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Roth, M. Mittelbronn, W. Wick, R. Meyermann, M. Tatagiba, and M. Weller
Malignant Glioma Cells Counteract Antitumor Immune Responses through Expression of Lectin-Like Transcript-1
Cancer Res., April 15, 2007; 67(8): 3540 - 3544.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
P. Tomasec, E. C. Y. Wang, V. Groh, T. Spies, B. P. McSharry, R. J. Aicheler, R. J. Stanton, and G. W. G. Wilkinson
Adenovirus vector delivery stimulates natural killer cell recognition
J. Gen. Virol., April 1, 2007; 88(4): 1103 - 1108.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. G. Iliopoulou, M. V. Karamouzis, I. Missitzis, A. Ardavanis, N. N. Sotiriadou, C. N. Baxevanis, G. Rigatos, M. Papamichail, and S. A. Perez
Increased Frequency of CD4+ Cells Expressing CD161 in Cancer Patients
Clin. Cancer Res., December 1, 2006; 12(23): 6901 - 6909.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
F. Gays, J. G. Aust, D. M. Reid, J. Falconer, N. Toyama-Sorimachi, P. R. Taylor, and C. G. Brooks
Ly49B Is Expressed on Multiple Subpopulations of Myeloid Cells
J. Immunol., November 1, 2006; 177(9): 5840 - 5851.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. A. Campillo, J. A. Martinez-Escribano, M. R. Moya-Quiles, L. A. Marin, M. Muro, N. Guerra, A. Parrado, M. Campos, J. F. Frias, A. Minguela, et al.
Natural Killer Receptors on CD8 T Cells and Natural Killer Cells from Different HLA-C Phenotypes in Melanoma Patients.
Clin. Cancer Res., August 15, 2006; 12(16): 4822 - 4831.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. R. Carlyle, A. Mesci, B. Ljutic, S. Belanger, L.-H. Tai, E. Rousselle, A. D. Troke, M.-F. Proteau, and A. P. Makrigiannis
Molecular and Genetic Basis for Strain-Dependent NK1.1 Alloreactivity of Mouse NK Cells.
J. Immunol., June 15, 2006; 176(12): 7511 - 7524.
[Abstract] [Full Text] [PDF]

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