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A receptor ligand system that can facilitate the unconditional killing of epithelial tumour cells by a subset of tumour infiltrating lymphocytes has been reported by a group at the Fred Hutchinson Cancer Research Centre, Seattle.1
We have known for many years that a subset of γ/δ T cells is specifically associated with immune responses at epithelial surfaces. Whereas γ/δ T cells in the blood predominantly use the Vδ2 delta chain, recognising soluble non-peptide antigens, the intraepithelial γ/δ T cells use the alternative Vδ1. Until quite recently there was no known ligand for these cells. Earlier work by this group, which has previously been highlighted inGut,2 3 demonstrated that these Vδ1 bearing cells recognise the ligands MICA and the closely related MICB, molecules which are distantly related to MHC class I but do not present intracellular peptide antigens. MICA is expressed patchily in normal gut epithelium, possibly induced in response to cellular distress, but not by other normal epithelia. It was therefore hypothesised that γ/δ T cells using Vδ1 patrol the gut, lysing those epithelial cells expressing MICA/B as a consequence of antigenic or chemical …