Mutations of the T-cell receptor constant region after in utero stem cell transplantation.
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.
Pirovano
Silvia
S
Laboratorio di Biotecnologie, Terzo Servizio Analisi, Piazzale Spedali Civili 1, Brescia, Italy.
Notarangelo
Luigi Daniele
LD
Valotti
Monica
M
Ugazio
Alberto G
AG
Albertini
Alberto
A
Imberti
Luisa
L
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
D007127:Immunoglobulin Constant Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta