Development of a coordinated allo T cell and auto B cell response against autosomal PTK2B after allogeneic hematopoietic stem cell transplantation

Haematologica. 2014 Feb;99(2):365-9. doi: 10.3324/haematol.2013.086652. Epub 2013 Oct 4.

Abstract

It is well known that allo-reactive T cells play a crucial role in graft-versus-leukemia and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (alloSCT). Allo-reactive CD4(+) T cells can mediate direct cytolysis, but may also stimulate production of IgG antibodies as helper cells. Immune complexes may subsequently be processed and presented by professional antigen presenting cells and stimulate induction of specific CD8(+) T cells. As such, proteins targeted in coordinated T- and B-cell responses may represent a class of immunodominant antigens in clinical responses after alloSCT. We previously identified LB-PTK2B-1T as HLA class II restricted polymorphic antigen in a patient treated with donor lymphocyte infusion for relapsed chronic myeloid leukemia after HLA-matched alloSCT. Since PTK2B has also been described as antibody target, we here investigated whether a coordinated T- and B-cell response against PTK2B was induced. Patient serum before and after alloSCT and donor lymphocyte infusion (DLI) was screened for antibodies, and we indeed observed development of a humoral immune response against PTK2B. Antibodies against PTK2B were only found after DLI and, in contrast to the CD4(+) T cells, recognized a monomorphic region of the protein. To our knowledge, this is the first description of a coordinated allo-reactive CD4(+) T-cell and auto-reactive antibody response against an autosomal antigen.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Female
  • Focal Adhesion Kinase 2 / genetics
  • Focal Adhesion Kinase 2 / immunology*
  • Focal Adhesion Kinase 2 / metabolism
  • Graft vs Host Disease / enzymology
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Isoantibodies / blood
  • Isoantibodies / immunology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / therapy
  • Male

Substances

  • Histocompatibility Antigens Class II
  • Immunoglobulin G
  • Isoantibodies
  • Focal Adhesion Kinase 2
  • PTK2B protein, human