Cross-reactive T-cell receptors in tumor and paraneoplastic target tissue.

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.