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Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria
- Source :
- Blood; June 2007, Vol. 109 Issue: 11 p5036-5042, 7p
- Publication Year :
- 2007
-
Abstract
- Deficiency of glycosylphosphatidylinositol (GPI)–anchored molecules on blood cells accounts for most features of paroxysmal nocturnal hemoglobinuria (PNH) but not for the expansion of PNH (GPI−) clone(s). A plausible model is that PNH clones expand by escaping negative selection exerted by autoreactive T cells against normal (GPI+) hematopoiesis. By a systematic analysis of T-cell receptor beta (TCR-β) clonotypes of the CD8+CD57+T-cell population, frequently deranged in PNH, we show recurrent clonotypes in PNH patients but not in healthy controls: 11 of 16 patients shared at least 1 of 5 clonotypes, and a set of closely related clonotypes was present in 9 patients. The presence of T-cell clones bearing a set of highly homologous TCR-β molecules in most patients with hemolytic PNH is consistent with an immune process driven by the same (or similar) antigen(s)—probably a nonpeptide antigen, because patients sharing clonotypes do not all share identical HLA alleles. These data confirm that CD8+CD57+T cells play a role in PNH pathogenesis and provide strong new support to the hypothesis that the expansion of the GPI−blood cell population in PNH is due to selective damage to normal hematopoiesis mediated by an autoimmune attack against a nonpeptide antigen(s) that could be the GPI anchor itself.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 109
- Issue :
- 11
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs57062547
- Full Text :
- https://doi.org/10.1182/blood-2006-10-052381