High affinity soluble ILT2 receptor: a potent inhibitor of CD8(+) T cell activation
Protein & Cell
;
(12): 1118-1127, 2010.
Artigo
em Inglês
| WPRIM
| ID: wpr-757675
ABSTRACT
Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Polietilenoglicóis
/
Ligação Proteica
/
Bioensaio
/
Proteínas Recombinantes de Fusão
/
Imunoglobulinas
/
Dados de Sequência Molecular
/
Cinética
/
Ativação Linfocitária
/
Receptores Imunológicos
Limite:
Humanos
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2010
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS