T-cell receptor analysis in Omenn's syndrome: Evidence for defects in generearrangement and assembly

Patients with Omenn's syndrome have a form of severe immune deficiency that is associated with pathological features of graft-versus-host disease, exc ept for the lack of foreign engraftment. It has been hypothesized that the disease's unique clinical features are mediated by an expanded population o f autologous self-reactive T cells of limited clonality. In the current stu dy, an investigation of the T-cell receptor (TCR) repertoire was undertaken to identify defects in T-cell rearrangement and development. The TCR reper toire in this group of patients was exquisitely restricted in the number of different TCR clonotypes, and some of these clonotypes seemed to have simi lar recognition motifs in the antigen-binding region, indicating antigen-dr iven proliferation of T lymphocytes. The TCRs from some patients lacked N- or P-nucleotide insertions and used proximal variable and joining gene segm ents, suggesting abnormal intrathymic T-cell development. Finally, abnormal assembly of gene segments and truncated rearrangements within nonproductiv e alleles suggested abnormalities in TCR rearrangement mechanisms. Overall, the findings suggest that inefficient and/or abnormal generation of TCRs m ay be a consistent feature of this disease. (C) 1999 by The American Societ y of Hematology.