Wednesday, October 14, 2009

NKT cells

As we know that natural killer (NK) cells are lymphocytes that play a major role in body's immune response to tumors and viruses. These are cytotoxic cells and constitute third kind of cells differentiated from common lymphocyte progenitor, which also generates B and T cells. NK cells kill tumor and virus infected cells by releasing perforins and granazyme contained in small cytoplasmic granules. These proteins cause the target cell to die by apoptosis. They do not express TCR or CD3 or BCR. Instead they express CD16 and CD56 in humans. Up to 80% NK cells also express CD8 (Wikipedia).

NKT cells on the other hand are T cells having properties of both T cells and NK cells. They express alpha beta TCR and other molecular markers associated with NK cells. They differ from T cells in that they response to glycolipid antigen presented by a cell surface molecule CD1d, which is related to MHC class I molecules. They do not respond to peptide antigens presented by MHC molecules. Thus, NKT cells are defined as a T cell lineage expressing NK lineage receptors including Cd1d-restricted alpha beta TCR. When NKT cells are activated, they produce Th1 (IFN-gamma) and Th2 (IL-4 and IL-13) cytokines. They are thought to provide quick help for a cell mediate immune response (IFN-gamma) or antibody mediated immune response (IL-4) and work as a link between innate and adaptive immune response. The deficiency or dysfunction of NKT cells has been implicated in many conditions such as diabetes and cancers. NKT cells are further divided into three types based on the molecules expressed on their surface. These are:

Type 1 NKT cells: Also called classical or invariant or Valpha 14i (mouse)/Valpha24i (human) NKT cells (iNKT). Their TCR is Valpha14-Jalpha18 in mice and Valpha24-Jalpha18 in humans. They also recognize the exogenous NKT cell ligands e.g. marine sponge derived alpha-galactosylceramides (alphaGalCer) and alpha-glycuronylceramide, which is a glycolipid that substitute for LPS in the cell wall of Gram negative bacteria, LPS negative bacteria such as Sphingomonas as well as self antigen isoglobotrihexosylceramide (iGb3). Their TCR is Cd1d restricted (BendelacA, savage PB, Teyton L. The biology of NKT cells. Annu. rev. Immunol. 200725:297-336.).

Type 2 NKT cells: Also called non-classical or diverse or non Valpha14 or non Valpha24 NKT. They do not have valpha14 or Valpha24. But they have other TCR markers. The foreign and self antigens recognized by these cells remain to be identified. Their TCR is also Cd1d restricted.

NKT like cells: They are also called NK1.1+ T cells or CD3+ CD56+ T cells. They are independent of Cd1d restriction. They do not have Valpha14 or Valpha24. Instead their TCR is Valpha7.2-Jalpha33 (humans) and Valpha19 (mouse).