HLA-class I-specific inhibitory receptors in human cytolytic T lymphocytes: Molecular characterization, distribution in lymphoid tissues and co-expression by individual T cells

A subset of cytolytic T lymphocytes has been shown to express receptors of the NK type (NKR) which can inhibit T cell cytotoxicity induced via the TCR-CD3 pathway. In this study, by the analysis of full length cDNA amplified from representative T cell clones, we show that NKR belonging either to the Ig superfamily, including p58.1, p58.2, p70 and p140, or to the C-type lectin superfamily (CD94/NKG2A), display sequences which are identical to those of the corresponding NKR expressed by CD3(-) NK cells. Moreover, a fragment of cDNA encoding the NKG2A protein was consistently amplified from all CD94(+) T cell clones analyzed. Since different NKR types can be expressed by T cells, we analyzed whether individual T cells could co-express more than one NKR. Analysis of either resting or activated (and cultured) T cell populations revealed that two or more NKR can be co-expressed by single T cells. Moreover, by the analysis of T cell clones, we show that co-expressed receptors are functional and can inhibit independently the TCR-induced cytolytic function. Finally, we investigated whether NKR+ T lymphocytes were also present in lymphoid tissues. No such cells were found in thymus or cord blood, thus further supporting the notion that they represent memory T cells. On the other hand, they were present in all the peripheral tissues analyzed including spleen, lymph nodes and tonsils.