title: Mutations of the T-cell receptor constant region after in utero stem cell transplantation.
abstract: Like the immunoglobulin genes, the T-cell receptor genes are generated by rearrangements of non-contiguous genomic V, D and J regions, but unlike the immunoglobulin genes, somatic hypermutation is an infrequent event in T-cell receptor genes. Here, we describe the occurrence of spontaneous mutations in the constant regions of the T-cell receptor beta chains of T lymphocytes obtained from two babies who underwent in utero transplantation because of severe combined immunodeficiency. In view of the fact that in babies receiving transplants before birth, hematopoietic chimerism is consistently present, the lymphocytes are likely to be under chronic activation, which may represent a relevant biologic stimulus for generating the observed T-cell receptor hypermutation. This possibility is supported by the finding that the highest number of mutations was identified in clonally expanded T cells. These results provide further support indicating that hypermutation of the T-cell receptor genes may indeed occur, given the necessary conditions.
authors.affiliation: Laboratorio di Biotecnologie, Terzo Servizio Analisi, Piazzale Spedali Civili 1, Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pirovano
authors.forename: Luigi Daniele
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Monica
authors.initials: M
authors.lastname: Valotti
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Ugazio
authors.forename: Alberto
authors.initials: A
authors.lastname: Albertini
authors.forename: Luisa
authors.initials: L
authors.lastname: Imberti
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D005333:Fetus / Q000601:surgery; D005787:Gene Frequency; D019674:Genes, T-Cell Receptor beta; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D016511:Severe Combined Immunodeficiency / Q000601:surgery; D014599:Uterus
chemical_list: D007127:Immunoglobulin Constant Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta