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

Abstract

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 β 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. ©2009 American Medical Association. All rights reserved.