Exclusive TCRVbeta chain usage of ex vivo generated minor Histocompatibility antigen HA-1 specific cytotoxic T cells: implications for monitoring of immunotherapy of leukemia by TCRBV spectratyping

Hematol J. 2002;3(6):271-5. doi: 10.1038/sj.thj.6200197.

Abstract

Tissue expression of minor Histocompatibility antigens HA-1 and HA-2 is limited to the hematopoietic system. Therefore, ex vivo generated HA-1/HA-2 specific cytotoxic T lymphocytes (CTLs) can be applied for adoptive immunotherapy of relapsed leukemia after HLA-matched HA-1/HA-2 mismatched stem cell transplantation. Here we used T cell receptor beta variable chain (TCRBV) spectratyping and/or TCRBV sequencing to monitor the specific TCR usage in eleven HA-1/HA-2 CTLs that were induced ex vivo with peptide pulsed dendritic cells. The HA-2 induced CTLs used different TCRBV. In contrast, the development of HA-1 specific CTLs coincided with prominent skewing of TCRBV7 spectratypes. Sequencing of the TCRBV7 specific PCR products used by these ex vivo generated HA-1 CTLs revealed the exclusive usage of TCRBV7-9*03, identical to the TCRBV used by HA-1 specific CTLs induced in vivo after stem cell transplantation. Thus, monitoring of immunotherapy with HA-1 specific CTLs is now also feasible by TCRBV spectratyping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Coculture Techniques
  • Dendritic Cells / immunology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Histocompatibility
  • Humans
  • Immunotherapy, Adoptive / methods
  • Leukemia / therapy
  • Minor Histocompatibility Antigens / immunology*
  • Neoplasm Proteins / immunology
  • Oligopeptides / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Recurrence
  • Sequence Analysis, DNA
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • HA-1 antigen
  • HA-2 antigen
  • Minor Histocompatibility Antigens
  • Neoplasm Proteins
  • Oligopeptides
  • Receptors, Antigen, T-Cell, alpha-beta