Abstract
The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate the V(D)J recombination process, which ultimately enables the generation of T cells and B cells with a diversified repertoire of antigen-specific receptors. Mutations of the RAG genes in humans are associated with a broad spectrum of clinical phenotypes, ranging from severe combined immunodeficiency to autoimmunity. Recently, novel insights into the phenotypic diversity of this disease have been provided by resolving the crystal structure of the RAG complex, by developing novel assays to test recombination activity of the mutant RAG proteins and by characterizing the molecular and cellular basis of immune dysregulation in patients with RAG deficiency.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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B-Lymphocytes / immunology*
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DNA-Binding Proteins / genetics*
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Genetic Therapy
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Homeodomain Proteins / genetics*
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Humans
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Immunologic Deficiency Syndromes / genetics
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Immunologic Deficiency Syndromes / immunology
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Immunologic Deficiency Syndromes / therapy
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Mutation
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Nuclear Proteins / genetics*
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Phenotype
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Severe Combined Immunodeficiency / genetics*
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Severe Combined Immunodeficiency / immunology
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Severe Combined Immunodeficiency / therapy
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T-Lymphocytes / immunology*
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V(D)J Recombination / genetics
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V(D)J Recombination / immunology*
Substances
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DNA-Binding Proteins
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Homeodomain Proteins
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Nuclear Proteins
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RAG2 protein, human
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RAG-1 protein