Cross-reactive T-cell receptors in tumor and paraneoplastic target tissue
Hannah L Pellkofer1, Raymond Voltz, Norbert Goebels
1Institute of Clinical Neuroimmunology,University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Background:
According to established criteria, paraneoplastic encephalomyelitis with adrenal neuroblastoma comprises a definite paraneoplastic neurologic syndrome.
Objective:
To detect T-cell clones that cross-react against antigens shared between tumor and nervous system.
Design:
Case study.
Setting:
Academic research. Patient A 22-year-old woman having paraneoplastic encephalomyelitis with adrenal neuroblastoma.
Main Outcome Measures:
We compared the T-cell receptor repertoires expressed in blood, cerebrospinal fluid, and neuroblastoma tumor tissue using complementary determining region 3 (CDR3) spectratyping and clone-specific polymerase chain reaction.
Results:
The T-cell receptor repertoire in cerebrospinal fluid was narrow compared with that in tumor and blood. Four T-cell clones from different tissues had identical T-cell receptor beta chains. Remarkably, the chains showed identical amino acid sequences but different nucleotide sequences.
Conclusions:
These T cells represent ontogenetically distinct clones but share functionally identical receptors. They recognize the same antigen in nervous system and tumor tissue and represent an attractive target for selective therapy.
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