Peptide Binding and Presentation by Mouse CD1

Castaño, A. Raúl; Tangri, Shabnam; Miller, J. E. W.; Holcombe, Hilda; Jackson, Michael R.; Huse, William D.; Kronenberg, Mitchell; Peterson, Per A.

doi:10.1126/science.7542403

Cited by 239 publications

(132 citation statements)

References 28 publications

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“…Although CD4 ϩ and DN NKT populations may harbor shared TCR specificities, there may be important differences between the two cell types. In normal mice, we have demonstrated that DN, but not CD4 ϩ , NKT cells of spleen and liver express inhibitory NK markers of the Ly-49 type, 4 and it has been reported that IL-4 production upon stimulation was found preferentially in the CD4 ϩ subset (Ref. 12 and M. Sköld and S. Cardell, manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

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CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR

Sköld

Faizunnessa

Wang

et al. 2000

The Journal of Immunology

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The majority of T lymphocytes carrying the NK cell marker NK1.1 (NKT cells) depend on the CD1d molecule for their development and are distinguished by their potent capacity to rapidly secrete cytokines upon activation. A substantial fraction of NKT cells express a restricted TCR repertiore using an invariant TCR Vα14-Jα281 rearrangement and a limited set of TCR Vβ segments, implying recognition of a limited set of CD1d-associated ligands. A second group of CD1d-reactive T cells use diverse TCR potentially recognizing a larger diversity of ligands presented on CD1d. In TCR-transgenic mice carrying rearranged TCR genes from a CD1d-reactive T cell with the diverse type receptor (using Vα3.2/Vβ9 rearrangements), the majority of T cells expressing the transgenic TCR had the typical phenotype of NKT cells. They expressed NK1.1, CD122, intermediate TCR levels, and markers indicating previous activation and were CD4/CD8 double negative or CD4+. Upon activation in vitro, the cells secreted large amounts of IL-4 and IFN-γ, a characteristic of NKT cells. In mice lacking CD1d, TCR-transgenic cells with the NKT phenotype were absent. This demonstrates that a CD1d-reactive TCR of the “non-Vα 14” diverse type can, in a ligand-dependent way, direct development of NK1.1+ T cells expressing expected functional and cell-surface phenotype characteristics.

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Section: Discussionmentioning

confidence: 99%

“…The CD1 molecules, unlike conventional MHC molecules, present lipids and glycolipids (1)(2)(3), as well as peptides (4,5), to T lymphocytes. In the mouse, different types of TCR␣␤ ϩ T cells have been described that recognize CD1d in the absence of added Ag (6 -10).…”

mentioning

confidence: 99%

CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR

Sköld

Faizunnessa

Wang

et al. 2000

The Journal of Immunology

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“…The production and purification of soluble recombinant mCD1 from D. melanogaster tissue culture cells were previously described (57). Purified mCD1 protein was incubated for 12 h at room temperature with a 3-fold molar excess of ␣-GalCer.…”

Section: Preparation and Use Of ␣-Galcer Mouse Cd1 Dimersmentioning

confidence: 99%

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

Elewaut¹,

Brossay²,

Santee

et al. 2000

The Journal of Immunology

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The development of lymphoid organs requires membrane-bound lymphotoxin (LT), a heterotrimer containing LTα and LTβ, but the effects of LT on T cell function have not been characterized extensively. Upon TCR cross-linking in vitro, splenocytes from both LTα−/− and LTβ−/− mice failed to produce IL-4 and IL-10 due to a reduction in NK T cells. Concordantly, LTα−/− and LTβ−/− mice did not respond to the lipoglycan α-galactosylceramide, which is presented by mouse CD1 to Vα14+ NK T cells. Interestingly, both populations of NK T cells, including those that are mouse CD1 dependent and α-galactosylceramide reactive and those that are not, were affected by disruption of the LTα and LTβ genes. NK T cells were not affected, however, in transgenic mice in which LT signaling is blocked, beginning on day 3 after birth, by expression of a soluble decoy LTβ receptor. This suggests that membrane-bound LT is critical for NK T cells early in ontogeny, but not for the homeostasis of mature cells.

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“…Perhaps reflecting the bias of the times, hydrophobic peptides (selected from random peptide libraries) were initially proposed to associate with CD1d [37] but were never shown to be recognized by iNKT cells.…”

Section: The Elusive Inkt Ligandmentioning

confidence: 99%

NKT cells: In the beginning…

MacDonald

2007

Eur. J. Immunol.

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Invariant natural killer T (iNKT) cells as we know them today are a unique subset of mature T cells co-expressing a semi-invariant Va14/Vb8 TCR and surface markers characteristic of NK cells. The semi-invariant TCR on iNKT cells recognizes glycolipids bound to monomorphic CD1d molecules, leading to rapid cytokine production. The purpose of this historical perspective is to describe how a series of seemingly unrelated findings in the late 1980s and early 1990s crystallized in the discovery of iNKT cells. The story is told from a personal viewpoint, with a particular effort to place both breakthroughs and misinterpretations in the context of their era. IntroductionIn the summer of 1987 two groups independently reported the identification of a mysterious subset of CD4 -CD8 -(double-negative, DN) thymocytes that overexpress the TCR Vb8 gene segment [1,2]. A third report followed shortly thereafter [3]. Around the same time an unusual invariant TCR Va14-Ja18 rearrangement was cloned from a panel of keyhole limpet hemocyaninspecific suppressor T cell hybridomas [4,5]. Collectively these studies provided the first glimpse of what are now known as invariant natural killer T (iNKT) cells, but the road to that conclusion proved to be unusually long and winding. The purpose of this "historical" feature is to recount this process of discovery from a personal viewpoint, highlighting both breakthroughs and misinterpretations along the way. Vb8-biased DN thymocytesGiven that most iNKT cells express CD4 and are preferentially localized in the liver, it may seem surprising that they were first identified as a DN subset in the thymus. However, two independent sets of circumstances contributed to this discovery. First a number of groups, including our own, were actively dissecting thymus subsets in the mid 1980s using flow cytometry and a growing battery of monoclonal antibodies (mAb). It became clear from the work of Fowlkes and Mathieson [6] that the very small DN subset (2-3% of thymocytes) contained immature precursors capable of differentiating into all other thymus subsets. This finding prompted intense scrutiny of the DN population by most groups working on T cell development.The second key catalyst to the discovery of iNKT cells was the successful production of the first allotypic mAb to the TCR by the Kappler/Marrack [7] and Bevan [8] groups. Although the TCRb and TCRa chains had been molecularly cloned, by this time no mAb to Vb domains had been identified. By pure serendipity these mAb were both directed against the Vb8 domain that is dramatically over-represented among iNKT cells. Thus it rapidly became clear that the DN thymocyte subset had a TCR repertoire that was heavily biased towards Vb8 [1][2][3].With hindsight it is interesting to note that this first glimpse of iNKT cells was interpreted incorrectly by both groups that made the initial discovery. Based on the dogma that DN thymocytes were immature, we speculated that the Vb8-biased subset might arise from preferential usage of certain Vb domains early in deve...

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Peptide Binding and Presentation by Mouse CD1

Cited by 239 publications

References 28 publications

CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR

CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

NKT cells: In the beginning…

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