title: 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.
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.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. rmverdijk@lumc.nl
authors.forename: Rob M
authors.initials: RM
authors.lastname: Verdijk
authors.forename: Tuna
authors.initials: T
authors.lastname: Mutis
authors.forename: Martina
authors.initials: M
authors.lastname: Wilke
authors.forename: Jos
authors.initials: J
authors.lastname: Pool
authors.forename: Ellen
authors.initials: E
authors.lastname: Schrama
authors.forename: Anneke
authors.initials: A
authors.lastname: Brand
authors.forename: Els
authors.initials: E
authors.lastname: Goulmy
mesh_terms: D001483:Base Sequence; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006648:Histocompatibility; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007938:Leukemia / Q000628:therapy; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012008:Recurrence; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: C110615:HA-1 antigen; C080145:HA-2 antigen; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta