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 lg 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.
Mingari
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MC
Dipartimento di Oncologia Clinica e Sperimentale, Università di Genova, Italy.
Ponte
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Cantoni
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Vitale
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Schiavetti
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Bertone
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Bellomo
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Cappai
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Biassoni
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D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D037102:Lectins / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism*; D005810:Multigene Family / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
D018076:DNA, Complementary; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037102:Lectins; D011971:Receptors, Immunologic