Cutting edge: novel RNA ligands able to bind CD4 antigen and inhibit CD4+ T lymphocyte function.
The value of high affinity-specific reagents in immunology is exemplified by the use of mAbs. Recent in vitro selection methods suggested that oligonucleotides may provide a useful alternative, especially where Abs have been insufficient thus far. We used a systematic evolution of ligands by exponential enrichment (SELEX) procedure to derive high affinity oligonucleotide ligands (aptamers) recognizing CD4. These RNase-resistant aptamers bound with high affinity and specificity as demonstrated using BIAcore (Stevenage, U.K.) technology. They also bound native CD4 on rat lymphocytes and specifically interfered with labeling by high affinity mAbs. All aptamers recognized the same binding site in the CDR2-like region in domain 1 of CD4. The applicability of these aptamers for immunologic studies was clearly demonstrated by their ability to block a fully allogeneic MLR in a CD4-specific manner. The high affinity and stability of aptamers point to their value in the analysis and functional manipulation of the immune system.
Kraus
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Medical Research Council Cellular Immunology Unit, University of Oxford, United Kingdom.
James
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Barclay
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D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015374:Biosensing Techniques; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D009841:Oligonucleotides / Q000378:metabolism* / Q000494:pharmacology; D011685:Purine Nucleotides / Q000378:metabolism; D011742:Pyrimidine Nucleotides / Q000378:metabolism; D012313:RNA / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000378:metabolism; D012685:Sepharose
D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D008024:Ligands; D009841:Oligonucleotides; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D011994:Recombinant Proteins; D012313:RNA; D012685:Sepharose