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

Arch Neurol. 2009 May;66(5):655-8. doi: 10.1001/archneurol.2009.56.

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 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / blood
  • Adrenal Gland Neoplasms / cerebrospinal fluid
  • Adrenal Gland Neoplasms / immunology*
  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / classification
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cell Lineage / immunology
  • Clone Cells / immunology
  • Cross Reactions / immunology
  • Female
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Neuroblastoma / diagnosis
  • Neuroblastoma / immunology*
  • Neuroblastoma / physiopathology
  • Paraneoplastic Syndromes, Nervous System / blood
  • Paraneoplastic Syndromes, Nervous System / cerebrospinal fluid
  • Paraneoplastic Syndromes, Nervous System / immunology*
  • Receptors, Antigen, T-Cell / analysis*
  • Receptors, Antigen, T-Cell / classification
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / classification
  • T-Lymphocytes / immunology
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta