The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF, 130K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Robson MacDonald, H.
Right arrow Articles by Held, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Robson MacDonald, H.
Right arrow Articles by Held, W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/6/2109/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 12, June 15, 1998 2109-2114

Brief Definitive Reports

Developmentally Regulated Extinction of Ly-49 Receptor Expression Permits Maturation and Selection of NK1.1+ T Cells

H. Robson MacDonald, Rosemary K. Lees, and Werner Held

From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland


   Abstract
Top
 Abstract
Materials and Methods
 Results and Discussion
 References
 
Clonally distributed inhibitory receptors negatively regulate natural killer (NK) cell function via specific interactions with allelic forms of major histocompatibility complex (MHC) class I molecules. In the mouse, the Ly-49 family of inhibitory receptors is found not only on NK cells but also on a minor (NK1.1+) T cell subset. Using Ly-49 transgenic mice, we show here that the development of NK1.1+ T cells, in contrast to NK or conventional T cells, is impaired when their Ly-49 receptors engage self-MHC class I molecules. Impaired NK1.1+ T cell development in transgenic mice is associated with a failure to select the appropriate CD1-reactive T cell receptor repertoire. In normal mice, NK1.1+ T cell maturation is accompanied by extinction of Ly-49 receptor expression. Collectively, our data imply that developmentally regulated extinction of inhibitory MHC-specific receptors is required for normal NK1.1+ T cell maturation and selection.

Key Words: NK1.1+ T cells • Ly-49 • development • repertoire selection • Ly-49A transgenic mice

Address correspondence to H.R. MacDonald, Ludwig Institute for Cancer Research, Ch. des Boveresses 155, 1066 Epalinges, Switzerland. Phone: 41-21-692-59-89; Fax: 41-21-653-44-74; E-mail: hughrobson. macdonald{at}isrec.unil.ch

Natural killer (NK)1.1+ T cells (1–4) are an unusual subset of murine T cells that express a highly restricted TCR-{alpha}/β repertoire comprised of an invariant V{alpha}14-J{alpha}281 chain and a predominant Vβ domain (Vβ8.2). Successful development of NK1.1+ T cells requires that their canonical TCR interact with CD1, a nonclassical, MHC-like molecule encoded outside of the MHC gene complex (5–8). The developmental origin of NK1.1+ T cells is controversial; nevertheless, it is widely accepted that they originate in the thymus and migrate to peripheral tissues such as spleen and liver (4). Indeed, direct evidence for such a migration pattern has recently been obtained by in vivo adoptive transfer studies (9).

In contrast to conventional T cells, NK1.1+ T cells express several phenotypic markers usually associated with NK cells such as NK1.1, CD122, and Ly-49. Ly-49 is a multigene family (comprised of at least nine members, A–I) encoding homodimeric C-type lectin-like receptors that interact with specific alleles of MHC class I proteins (10). In NK cells, it has been clearly shown that Ly-49–MHC class I interaction negatively regulates effector functions such as cytotoxicity and bone marrow graft rejection (11, 12). Although conventional TCR-{alpha}/β cells in the mouse do not normally express Ly-49 receptors, studies of Ly-49A transgenic mice have demonstrated that proliferative responses of mature transgenic T cells to alloantigens can be specifically inhibited by appropriate Ly-49–MHC class I interactions (13), thus raising the possibility that signaling via the TCR is susceptible to a Ly-49–dependent regulatory mechanism. This hypothesis is further supported by recent data indicating that both cytokine secretion and the cytotoxicity of NK1.1+ T cells are specifically inhibited upon Ly-49–MHC class I interaction (14).

The potential ability of Ly-49 receptors to counteract signaling by the TCR could also be of physiological relevance for NK1.1+ T cell development. In this report, we have tested this hypothesis by comparing putatively immature (thymic) and mature (liver) NK1.1+ T cells in normal as well as Ly-49A transgenic mice. Our data indicate that developmentally regulated extinction of Ly-49 receptor expression is required to allow appropriate TCR repertoire selection and subsequent maturation of NK1.1+ T cells.


   Materials and Methods
Top
 Abstract
 Materials and Methods
Results and Discussion
 References
 
Mice.
C57BL/6 mice were obtained from Harlan Olac (Bicester, UK). Mice deficient for the transporter associated with antigen processing (TAP1–) on a C57BL/6 background (15) were obtained from The Jackson Laboratories (Bar Harbor, ME). The production of Ly-49A transgenic mice has been described previously (13). These mice were established on a (CBA/J x C57BL/ 6) F2 background and subsequently backcrossed to either C57BL/6 (H-2b) or B10.D2 (H-2d). Transgenic and littermate mice (fifth backcross) were analyzed in parallel.

Cells.
Liver mononuclear cells were prepared as previously described (16). Thymocytes were depleted of heat stable antigen (HSA)+ cells by treatment with rat IgM mAb B2A2 plus rabbit complement. Viable recovered cells (~1% of input) were purified on a lympholyte-M gradient (Cedarlane Labs., Hornby, Ontario, Canada).

Flow Microfluorometry.
HSAlow thymocytes or liver mononuclear cells were first incubated with unlabeled mAb 24G2 (anti–Fc receptor) to block nonspecific binding, and were then triple stained with combinations of the following mAb conjugates: anti-Ly49A-FITC (A1); anti–Ly-49C/I-FITC (5E6); anti-Ly-49G2-FITC (4D11); anti-V{alpha}2-FITC (B20.1); anti-V{alpha}3.2-FITC (RR3-16); anti-V{alpha}8-FITC (B21.14); anti-V{alpha}11-FITC (RR8-1); anti-Vβ8.2-FITC (F23.2); anti-NK1.1-PE (PK136); anti–TCR-{alpha}/β–biotin (H57-597); and anti-Ly49C-biotin (4LO-3311). The latter two mAbs were revealed with avidin-tricolor. All mAbs were obtained from PharMingen (San Diego, CA), with the exception of 4LO-3311 (17). Samples were passed on a FACScan® flow cytometer (Becton Dickinson, San Jose, CA) gated to exclude nonviable cells on the basis of light scatter. Data were analyzed by LYSIS II software.


   Results and Discussion
Top
 Abstract
 Materials and Methods
 Results and Discussion
References
 
Although NK1.1+ T cells are present in small numbers in other tissues, they have been primarily studied in thymus and liver, where they account for ~25% of mature (HSAlow) TCR-{alpha}/β cells in C57BL/6 mice (Fig. 1 A). Interestingly, analysis of expression of Ly-49A, Ly-49C/I, and Ly-49G2 (the only inhibitory Ly-49 family members for which mAbs are available) in these organs revealed that the proportion of NK1.1+ T cells expressing each of the Ly-49 genes was substantially (two- to fivefold) higher in thymus than in liver (Fig. 1 B). Conventional (i.e., NK1.1–) TCR-{alpha}/β cells did not express Ly-49 receptors to any significant degree (data not shown).


Figure 1
View larger version (26K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1 Differential expression of Ly-49 receptors by NK1.1+ T cells in thymus and liver. Thymocytes (HSAlow fraction) and liver mononuclear cells from normal C57BL/6 mice were triple stained with mAbs against NK1.1 and TCR-{alpha}/β, and Ly-49A, Ly-49C/I, or Ly-49G2. The cytograms in A depict NK1.1 versus TCR-{alpha}/β fluorescence. The mean percentage (± SD) of NK1.1+ T cells (upper right quadrant) is indicated. The histograms in B represent Ly-49A, Ly-49C/I, or Ly-49G2 staining gated on NK1.1+ TCR-{alpha}/β+ cells. Numbers represent the mean percentage of positive cells (± SD) in the indicated gates (5–10 experiments).

 
The reduced frequency of Ly-49+ NK1.1+ T cells in liver as compared to thymus of normal mice could reflect a requirement for loss of Ly-49 expression during NK1.1+ T cell maturation. To test this hypothesis we used a transgenic mouse strain (13) in which all thymic and liver NK1.1+ T cells express Ly-49A, as compared to the minor (10–20%) Ly-49A+ subset of NK1.1+ T cells in nontransgenic littermates (Fig. 2 A). Moreover, endogenous and transgenic Ly-49A were expressed at similar levels on NK1.1+ T cells (Fig. 2 A). As previously described (13), the transgene is also expressed on all NK and T cells. In C57BL/6 (H-2b) Ly-49A transgenic mice (where there is no ligand for Ly-49A), NK1.1+ T cells as well as T and NK cells develop normally in both thymus and liver as compared to nontransgenic littermates (Fig. 2 B).


Figure 2
View larger version (32K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2 Selectively impaired NK1.1+ T cell development in liver of H-2d Ly-49A transgenic mice. Thymocytes (HSAlow fraction) or liver mononuclear cells from Ly-49A transgenic mice or control littermates on a H-2b (C57BL/6) or H-2d (B10.D2) background were analyzed by three-color flow microfluorometry for expression of NK1.1, TCR-{alpha}/β, and Ly-49A. In A, Ly-49A fluorescence profiles gated on NK1.1+ TCR-{alpha}/β+ cells from normal (closed histograms) or transgenic (open histograms) mice are superimposed. The mean Ly-49A fluorescence intensity of the transgenic NK1.1+ T cells is indicated in each case. The cytograms in B depict NK1.1 versus TCR-{alpha}/β fluorescence. Numbers represent the mean percentage (± SD) of T cells (upper left), NK1.1+ T cells (upper right), and NK cells (lower right) in transgenic and littermate mice on an H-2b (n = 4) or H-2d (n = 7) background. The absolute numbers of HSAlow thymocytes (1–2 x 106) and liver mononuclear cells (4–5 x 106) did not differ significantly among the different groups of mice. The lower proportion of liver NK1.1+ T cells in H-2d versus H-2b littermate mice reflects differences between the C57BL/6 and C57BL/10 genetic backgrounds (data not shown).

 
To ascertain whether NK1.1+ T cell development is affected by Ly-49 engagement, we analyzed Ly-49A transgenic mice on a B10.D2 (H-2d) background where the ligand for Ly-49A (H-2Dd) is expressed. As shown in Fig. 2 A, the cell surface level of Ly-49A was downmodulated to a similar extent in NK1.1+ T cells of transgenic and wild-type H-2d (as compared to H-2b) mice. Similar results have been observed for NK cells in these and other Ly-49A transgenic mice (18). Importantly, both the frequency and absolute number of liver NK1.1+ T cells was significantly (threefold) reduced in H-2d Ly-49A transgenic mice as compared to nontransgenic littermates (Fig. 2 B). This effect was specific for the NK1.1+ T cell lineage since both NK cells and conventional (NK1.1–) T cells developed normally in the liver of H-2d mice despite expression of the Ly-49A transgene (Fig. 2 B). In the thymus, only a modest reduction of NK1.1+ T cells was observed in H-2d Ly-49A transgenic mice as compared to littermates (Fig. 2 B).

If Ly-49 engagement in fact modifies signaling via the TCR, then the impaired development of NK1.1+ T cells in H-2d Ly-49A transgenic mice might reflect a failure to select the highly restricted CD1-specific TCR repertoire. To address this issue, we compared TCR V{alpha} and Vβ use in these mice with nontransgenic littermates. In normal mice, NK1.1+ T cells in thymus and liver exhibit a TCR repertoire that is highly skewed to V{alpha}14 and Vβ8.2 (1–4). Since no reliable mAb to V{alpha}14 is currently available, we assessed V{alpha}14 skewing in NK1.1+ T cells using a pool of four anti-V{alpha} mAbs that together detect 20–25% of the normal TCR V{alpha} repertoire. As shown in Fig. 3, both thymic and liver NK1.1+ T cells from control H-2d littermates had a very high proportion of Vβ8.2+ cells and very few cells staining with the V{alpha} mAb panel, as would be expected for cells expressing the canonical V{alpha}14/Vβ8.2 TCR. Remarkably, however, liver NK1.1+ T cells from H-2d Ly-49A transgenic mice exhibited much lower levels of Vβ8.2+ cells and much higher levels of cells expressing the V{alpha} panel. Indeed, the V{alpha} and Vβ repertoires of liver NK1.1+ T cells in these mice were not significantly different from those of conventional (NK1.1–) liver T cells (Fig. 3 B), indicating that the small proportion of NK1.1+ T cells that was still able to develop despite the presence of a self-MHC–reactive Ly-49 receptor did not express the canonical V{alpha}14/Vβ8.2 TCR.


Figure 3
View larger version (18K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3 Altered TCR repertoire selection in NK1.1+ T cells from H-2d Ly-49A transgenic mice. NK1.1+ TCR-{alpha}/β+ cells from thymus or liver of Ly-49A transgenic (Tg) mice and their littermate (LM) or wild-type (WT) controls on either an H-2b or H-2d genetic background (gated as in Fig. 2) were analyzed in the third color for expression of Vβ8.2 or V{alpha} (pool of V{alpha}2, V{alpha}3.2, V{alpha}8, and V{alpha}11). Histograms in A show representative Vβ8.2 and V{alpha} staining patterns gated on liver NK1.1+ T cells from H-2d mice. Data in B represent the mean percentage (± SD) of Vβ8.2+ or V{alpha}+ cells among NK1.1+ T cells (black bars) or conventional T cells (gray bars) in the indicated groups of mice (3–6 mice per group). Where no error bars are indicated, the results represent the mean of two mice.

 
In the thymus of H-2d Ly-49A transgenic mice, the skewing towards Vβ8.2 and V{alpha}14 in NK1.1+ T cells was reduced compared with littermate controls, but still highly significant when compared with conventional (NK1.1–) T cells (Fig. 3 B). Thus, most thymic NK1.1+ T cells bearing the self-MHC–reactive Ly-49 receptor still expressed the canonical TCR, whereas a minority did not. Perturbations in the TCR V{alpha} and Vβ repertoires of NK1.1+ T cells were strictly dependent upon Ly-49A–ligand interactions and not related to expression of the transgene per se, since NK1.1+ T cells from the liver and thymus of H-2b Ly-49A transgenic mice were indistinguishable from their nontransgenic littermates in terms of Vβ8.2 and V{alpha} staining (Fig. 3 B).

Taken together, our data with Ly-49A transgenic mice provide direct evidence that the development of NK1.1+ T cells expressing self–MHC class–I-reactive Ly-49 receptors is selectively impaired. Moreover, impaired development of NK1.1+ T cells is clearly correlated with a failure to select the CD1-reactive canonical TCR, strongly arguing that TCR signaling is perturbed by Ly-49 engagement in this lineage. The molecular mechanism responsible for impaired TCR signaling by NK1.1+ T cells in Ly-49A transgenic mice is currently unknown; however, by analogy with signaling events in NK cells (19–21) and conventional T cells (22, 23), it is tempting to speculate that dephosphorylation of TCR-associated protein kinases (such as ZAP-70) in NK1.1+ T cells by Ly-49–associated phosphatases (such as SHP-1) leads to reduced TCR signaling upon CD1 engagement, and hence to the lack of further maturation.

Comparison of our data on normal and Ly-49A transgenic mice leads to a novel model for the regulation of Ly-49 receptor expression during NK1.1+ T cell development. According to this scenario, immature NK1.1+ T cells expressing self-reactive Ly-49 receptors initially develop in the thymus. However subsequent maturation of these cells (and/or their export to peripheral tissues such as the liver) requires loss of Ly-49 expression to avoid interference with TCR signaling if Ly-49 receptors are engaged. Two distinct mechanisms could account for loss of Ly-49 receptor expression during NK1.1+ T cell maturation. One possibility would be that Ly-49 expression is simply extinguished in a developmentally regulated and lineage-specific fashion. Alternatively, selection against NK1.1+ T cells expressing self-MHC–reactive Ly-49 receptors may occur.

Direct evidence that Ly-49 receptors are switched off during normal NK1.1+ T cell development was obtained in TAP1– mice (15, 24), which express CD1 (the positively selecting ligand for the canonical TCR on NK1.1+ T cells), but not MHC class I (the ligand for Ly-49 inhibitory receptors). Consistent with earlier studies (25, 26), the frequency of NK1.1+ T cells in thymus and liver of TAP1– mice (36 and 28%, respectively) was comparable with that in wild-type controls. More importantly, the proportion of NK1.1+ T cells expressing Ly-49A, Ly-49C, and Ly-49G2 was reduced fivefold in liver (as compared with thymus) of TAP1– mice (Fig. 4), similar to what had been observed for wild-type mice (Fig. 1 B). Since all potential selecting ligands for Ly-49 receptors are presumably absent in TAP1– mice, these data argue definitively that extinction of Ly-49 receptor expression must be occurring during normal NK1.1+ T cell development.


Figure 4
View larger version (24K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4 Differential Ly-49 receptor expression by NK1.1+ T cells in thymus and liver occurs independently of MHC class I. Thymocytes (HSAlow fraction) and liver mononuclear cells from TAP1– mice were triple stained with mAbs against NK1.1 and TCR-{alpha}/β, and Ly-49A, Ly-49C, or Ly-49 G2. Data are expressed as the mean percentage of Ly-49+ cells among NK1.1+ TCR-{alpha}/β+ cells (2 mice per group).

 
In conclusion, our data point to a novel lineage-specific role and regulation of Ly-49 receptor expression during normal NK1.1+ T cell development. Although immature NK1.1+ T cells expressing self–MHC class I–reactive Ly-49 receptors extinguish Ly-49 expression in the course of their maturation, NK cells do not. This dichotomy may reflect a fundamental difference not only in the development, but also in the function, of these two lymphocyte lineages. Thus, mature NK cells are generally believed to require expression of at least one self-reactive Ly-49 inhibitory receptor to avoid potential autoreactivity and to facilitate surveillance of tissues rendered MHC class I–deficient by infection or transformation (27). On the other hand, mature NK1.1+ T cells, which recognize CD1 (probably in association with a glycolipid; reference 28) via their canonical TCR, may need to extinguish the expression of self-reactive Ly-49 inhibitory receptors so that they can be activated optimally by foreign antigens in any normal (i.e., MHC class I–expressing) tissue.

Finally, in a more philosophical vein, one might ask why Ly-49 receptors are expressed at all in the NK1.1+ T cell lineage if their subsequent extinction is required for correct NK1.1+ T cell maturation. One rather trivial explanation would be that transient expression of Ly-49 receptors in the NK1.1+ T cell lineage represents an "evolutionary accident" resulting from a (hypothetical) close developmental relationship to NK cells. Alternatively, Ly-49 receptor engagement may play some positive role early in NK1.1+ T cell development, as suggested by the fact that some Ly-49 receptor family members (such as Ly-49D) have activating properties (29). The third (and perhaps most interesting) possibility could be that the presence of inhibitory Ly-49 receptors on NK1.1+ T cells may be required at a particular stage of development to establish a correct threshold for activating signals delivered by the TCR or other (as yet unidentified) receptors. In the latter context, it is interesting that inefficient development of "NK1.1-like" T cells expressing the canonical CD1-reactive TCR can occur in the absence of Ly-49 (and NK1.1) expression in the thymus of mice rendered deficient for the common cytokine {gamma} chain (30). However, these cells are not found in peripheral tissues such as the liver, consistent with the possibility that early Ly-49 expression may be necessary for efficient and/or complete NK1.1+ T cell development.


   Acknowledgments
 
We thank Dr. Suzanne Lemieux (Institut Armand-Frappier, Montreal, Canada) for the 4L0-3311 mAb and Anna Zoppi for preparation of the manuscript.

Submitted: 12 March 1998

Werner Held was supported by a grant (31-49137.96) and a START (Swiss Talents for Academic Research and Teaching) fellowship from the Swiss National Science Foundation.


   References
Top
 Abstract
 Materials and Methods
 Results and Discussion
 References
 

1 MacDonald HR. NK1.1+ T cell receptor {alpha}β+cells: new clues to their origin, specificity and function, J Exp Med, 1995, 182, 633–638.[Free Full Text]

2 Bix M & Locksley RM. Natural T cells. Cells that co-express NKRP-1 and TCR, J Immunol, 1995, 155, 1020–1022.[Medline]

3 Vicari AP & Zlotnik A. Mouse NK1.1+T cells: a new family of T cells, Immunol Today, 1996, 17, 71–76.[Medline]

4 Bendelac A, Rivera MN, Park S-H & Roark JH. Mouse CD1-specific NK1 T cells: development, specificity and function, Annu Rev Immunol, 1997, 15, 535–562.[Medline]

5 Bendelac A, Lantz O, Quimby ME, Yewdell JW, Bennink JR & Brutkiewicz RR. CD1 recognition by mouse NK1+T lymphocytes, Science, 1995, 268, 863–865.[Abstract/Free Full Text]

6 Smiley ST, Kaplan MH & Grusby MJ. Immunoglobulin E production in the absence of interleukin-4–secreting CD1-dependent cells, Science, 1997, 275, 977–979.[Abstract/Free Full Text]

7 Chen Y-H, Chiu NM, Mandal M, Wang N & Wang C-R. Impaired NK1+T cell development and early IL-4 production in CD1-deficient mice, Immunity, 1997, 6, 459–467.[Medline]

8 Mendiratta SK, Martin WD, Hong S, Boesteanu A, Joyce S & Van Kaer L. CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4, Immunity, 1997, 6, 469–477.[Medline]

9 Schulz R-J, Parkes A, Mizoguchi E, Bhan AK & Koyasu S. Development of CD4– CD8– {alpha}βTCR+ NK1.1+T lymphocytes. Thymic selection by self antigen, J Immunol, 1996, 157, 4379–4389.[Abstract]

10 Yokoyama WM & Seaman WE. The Ly-49 and NKR-P1 gene families encoding lectin-like receptors on natural killer cells: the NK gene complex, Annu Rev Immunol, 1993, 11, 613–635.[Medline]

11 Karlhofer FM, Ribaudo RK & Yokoyama WM. MHC class I alloantigen specificity of Ly-49+IL-2 activated natural killer cells, Nature, 1992, 358, 66–70.[Medline]

12 Yu YY, George T, Dorfman JR, Roland J, Kumar V & Bennett M. The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts, Immunity, 1996, 4, 67–76.[Medline]

13 Held W, Cado D & Raulet DH. Transgenic expression of the Ly49A natural killer cell receptor confers class I major histocompatibility complex (MHC)-specific inhibition and prevents bone marrow allograft rejection, J Exp Med, 1996, 184, 2037–2041.[Abstract/Free Full Text]

14 Ortaldo JR, Winkler-Pickett R, Mason AT & Mason LH. The Ly-49 family: regulation of cytotoxicity and cytokine production in murine CD3+cells, J Immunol, 1998, 160, 1158–1165.[Abstract/Free Full Text]

15 Van Kaer L, Ashton-Rickardt PG, Ploegh HL & Tonegawa S. TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4–8+T cells, Cell, 1992, 71, 1205–1214.[Medline]

16 Ohteki T & MacDonald HR. Major histocompatibility complex class I related molecules control the development of CD4+8– and CD4–8– subsets of natural killer 1.1+ T cell receptor–{alpha}/β+cells in the liver of mice, J Exp Med, 1994, 180, 699–704.[Abstract/Free Full Text]

17 Gosselin P, Lusignan Y, Brennan J, Takei F & Lemieux S. The NK2.1 receptor is encoded by Ly-49C and its expression is regulated by MHC class I alleles, Int Immunol, 1997, 9, 533–540.[Abstract/Free Full Text]

18 Fahlén L, Khoo NKS, Daws MR & Sentman CL. Location-specific regulation of transgenic Ly49A receptors by major histocompatibility complex class I molecules, Eur J Immunol, 1997, 27, 2057–2065.[Medline]

19 Burshtyn DN, Scharenberg AM, Wagtmann N, Rajagopalan S, Berrada K, Yi T, Kinet JP & Long EO. Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor, Immunity, 1996, 4, 77–85.[Medline]

20 Fry AM, Lanier LL & Weiss A. Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C, J Exp Med, 1996, 184, 295–300.[Abstract/Free Full Text]

21 Olcese L, Lang P, Vély F, Cambiaggi A, Marguet D, Bléry M, Hippen KL, Biassoni R, Moretta A, Moretta L et al.. Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases, J Immunol, 1996, 156, 4531–4534.[Abstract]

22 Pani G, Fischer K-D, Mlinaric-Rascan I & Siminovitch KA. Signaling capacity of the T cell antigen receptor is negatively regulated by the PTP1C tyrosine phosphatase, J Exp Med, 1996, 184, 839–852.[Abstract/Free Full Text]

23 Plas DR, Johnson R, Pingel JT, Matthews RJ, Dalton M, Roy G, Chan AC & Thomas ML. Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling, Science, 1996, 272, 1173–1176.[Abstract]

24 Brutkiewicz RR, Bennink JR, Yewdell JW & Bendelac A. TAP-independent, β2-microglobulin–dependent surface expression of functional mouse CD1.1, J Exp Med, 1995, 182, 1913–1919.[Abstract/Free Full Text]

25 Adachi Y, Koseki H, Zijlstra M & Taniguchi M. Positive selection of invariant V{alpha}14+T cells by non-major histocompatibility complex–encoded class I–like molecules expressed on bone-marrow–derived cells, Proc Natl Acad Sci USA, 1995, 92, 1200–1204.[Abstract/Free Full Text]

26 Joyce S, Negishi I, Boesteanu A, DeSilva AD, Sharma P, Chorney MJ, Loh DY & Van Kaer L. Expansion of natural (NK1+) T cells that express {alpha}β T cell receptors in transporters associated with antigen presentation–1 null and thymus leukemia antigen positive mice, J Exp Med, 1996, 184, 1579–1584.[Abstract/Free Full Text]

27 Ljunggren HG & Kärre K. In search of the "missing self": MHC molecules and NK cell recognition, Immunol Today, 1990, 11, 237–244.[Medline]

28 Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E et al.. CD1d-restricted and TCR-mediated activation of V{alpha}14 NKT cells by glycosylceramides, Science, 1997, 278, 1626–1629.[Abstract/Free Full Text]

29 Mason LH, Anderson SK, Yokoyama WM, Smith HRC, Winkler-Pickett R & Ortaldo JR. The Ly-49D receptor activates murine natural killer cells, J Exp Med, 1996, 184, 2119–2128.[Abstract/Free Full Text]

30 Lantz O, Sharara LI, Tilloy F, Andersson A & DiSanto JP. Lineage relationships and differentiation of natural killer (NK) T cells: intrathymic selection and interleukin (IL)-4 production in the absence of NKR-P1 and Ly49 molecules, J Exp Med, 1997, 185, 1395–1401.[Abstract/Free Full Text]


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF, 130K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Robson MacDonald, H.
Right arrow Articles by Held, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Robson MacDonald, H.
Right arrow Articles by Held, W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS