cells expressing the ␥␦ T-cell receptor (TCR) display strong major histocompatibility complex (MHC)-unrestricted cytotoxicity against tumour cells when activated in vitro by interleukin 2 (IL-2) 1 . The cytotoxic activity of ␥␦ T cells is reminiscent of natural killer (NK) cells, which preferentially lyse target cells that have lost MHC class I alleles 2,3 -a frequent occurrence in tumour progression 4 . This 'missing self hypothesis' 2 has been explained by the discovery of inhibitory MHC class I receptors (INMRs) expressed by NK cells 3 and some ␥␦ and ␣ T cells 5,6 . INMRs bind to particular class I alleles and inhibit the killer cells' cytotoxic machinery against target cells expressing normal class I levels, but not against target cells with reduced class I expression.
Typically, 2-5% of lymphocytes in the peripheral blood of adults express the ␥␦ TCR (Ref. 7). Most of these ␥␦ T cells can be classified into the V␥9/V␦2 subset (up to 90% of blood ␥␦ T cells) or the V␦1 subset (up to 50%). Practically all V␥9/V␦2 T cells express INMRs (Refs 8, 9). The INMRs include different types of killer-cell inhibitory receptors (KIRs), members of the immunoglobulin superfamily, and the lectin-type receptors CD94-NKG2A and -B (Ref. 3). Expression of INMRs by ␥␦ T cells implies that these cells play a role in tumour defence similar to that suggested for NK cells. Moreover, expression of INMRs by cytotoxic ␥␦ T cells prevents autoimmunity, as exemplified by recent observations in a patient with pure red cell aplasia 10 .