Structural features of nonpeptide prenyl pyrophosphates that determine their antigenicity for human gamma delta T cells.
Human Vgamma2Vdelta2(+) T cells proliferate in vivo during many microbial infections. We have found that Vgamma2Vdelta2(+) T cells recognize nonpeptide prenyl pyrophosphates and alkylamines. We now have defined structural features that determine the antigenicity of prenyl pyrophosphates by testing synthetic analogs for bioactivity. We find that the carbon chain closest to the pyrophosphate moiety plays the major role in determining bioactivity. Changes in this area, such as the loss of a double bond, abrogated bioactivity. The loss of a phosphate from the pyrophosphate moiety also decreased antigenicity 100- to 200-fold. However, nucleotide monophosphates could be added with minimal changes in bioactivity. Longer prenyl pyrophosphates also retained bioactivity. Despite differences in CDR3 sequence, Vgamma2Vdelta2(+) clones and a transfectant responded similarly. Ag docking into a Vgamma2Vdelta2 TCR model reveals a potential binding site in germline regions of the Vgamma2Jgamma1.2 CDR3 and Vdelta2 CDR2 loops. Thus, Vgamma2Vdelta2(+) T cells recognize a core carbon chain and pyrophosphate moiety. This recognition is relatively unaffected by additions at distal positions to the core Ag unit.
Morita
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Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Group in Immunology, University of Iowa College of Medicine, Iowa City, IA 52242, USA. craig-morita@uiowa.edu
Lee
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Wang
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Li
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Mariuzza
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Tanaka
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D000328:Adult; D000941:Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D011756:Diphosphates / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045782:Hemiterpenes; D006801:Humans; D019169:Jurkat Cells; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D012717:Sesquiterpenes; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection
D000941:Antigens; D011756:Diphosphates; D018984:Epitopes, T-Lymphocyte; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D011106:Polyisoprenyl Phosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012717:Sesquiterpenes; C004809:isopentenyl pyrophosphate; C004808:farnesyl pyrophosphate; C002963:geranylgeranyl pyrophosphate