T-cell receptor V delta-J alpha rearrangements in human thymocytes: the role of V delta-J alpha rearrangements in T-cell receptor-delta gene deletion.
The differentiation mechanisms that force thymocytes into the T-cell receptor (TCR)-alpha beta or TCR-gamma delta lineage are poorly understood, but rearrangement processes in the TCR-alpha/delta locus are likely to play an important role. It is assumed that the TCR-delta gene is deleted prior to V alpha-J alpha rearrangements by rearrangement of the so-called TCR-delta-deleting elements delta Rec and psi J alpha. However, the TCR-delta gene can also be deleted via V delta-J alpha rearrangements. We studied the different TCR-delta-deleting rearrangements of V delta 1, delta Rec, V delta 2 and V delta 3 to J alpha gene segments in human thymocytes and peripheral blood using polymerase chain reaction analysis. The V delta 1 gene segment is the most upstream V delta gene segment tested and appears to rearrange to almost all J alpha gene segments. In contrast, the delta Rec and V delta 2 gene segments only rearrange to the 5'-located J alpha gene segments, thereby preserving an extensive TCR-alpha combinatorial diversity, because most J alpha gene segments are kept available for subsequent V alpha-J alpha rearrangements. Based on our combined data we hypothesize that the different V delta gene segments and the delta Rec gene segment play different roles in T-cell development with regard to TCR-delta deletion.
Verschuren
M C
MC
Department of Immunology, Erasmus University Rotterdam, The Netherlands.
Wolvers-Tettero
I L
IL
Breit
T M
TM
van Dongen
J J
JJ
D000293:Adolescent; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000276:immunology; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology*
D015345:Oligonucleotide Probes; D016692:Receptors, Antigen, T-Cell, gamma-delta