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NKT cells

Naturals Killer T cells (NKT cells) are a unique subset of lymphocytes that express markers of NK cells and a semi-invariant T cell receptor. In mice, NKT cells express the NK cell receptor NK1.1 (NKR-P1C, CD161), a member of the Ly-49 receptor family, and a TR with an invariant V-ALPHA domain, encoded by the TRAV11-TRAJ18 (previously Vα14-Jα281) rearrangement, in association with a highly skewed set of Vβ chains, most frequently TRBV13-2 (previously Vβ8.2) [1]. The TR of NKT cells recognizes glycolipids bound to the monomorphic MHC class I-like molecule CD1d, a member of the MhcSF. In the liver of normal mice, 20-30% of their lymphoid cells consist of NKT cells.

Although the endogenous and foreign glycolipids recognized by the TR on NKT cells are not known, a synthetic glycolipid (α-Galactosyl ceramide α-Galler) bound to CD1d mimics their effects. α-Galactosyl ceramide-activated Vα14 natural killer T cells mediate protection against murine malaria [2]. When activated, NKT cells secrete large amounts of cytokines, such as interferon-γ (INF-γ) and interleukin-4 (IL-4).

When expressed TR is an activating receptor that transduces positive signals through mobilization of intracellular kinases. In contrast, Ly-49 receptors are inhibitory receptors that recuit intracellular phosphatases.

In the thymus, rare CD4+8+ thymocytes expressing TR that bind to CD1d develop along the NKT cell lineage, first undergoing proliferation and then expressing inhibitory NKRs such as Ly-49. During this maturation process, the NKT cells evolve from a TH2 (IL-4>IFN-γ) to TH1 (IFN-γ>IL-4) pattern [3].

In human, the "invariant" TR alpha chain of the human CD161+ T cells which recognizes C1d results from the TRAV10-TRAJ18 (previously Vα24-JαQ) rearrangement.

[1] Lantz, O. and Bendelac, A J., Exp. Med., 180, 1097-1106 (1994)
[2] Gonzalez-Aseguinolaza, G. et al., Proc. Natl. Acad. Sci. USA, 97, 8461-8466 (2000).
[3] MacDonald, H.R., Science, 296, 481-482 (2002).
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