Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion

Clin Cancer Res. 2010 May 15;16(10):2729-39. doi: 10.1158/1078-0432.CCR-10-0415. Epub 2010 May 11.


Purpose: The target antigens of graft-versus-leukemia that are tumor associated are incompletely characterized.

Experimental design: We examined responses developing against CML66, an immunogenic antigen preferentially expressed in myeloid progenitor cells identified from a patient with chronic myelogenous leukemia who attained long-lived remission following CD4+ donor lymphocyte infusion (DLI).

Results: From this patient, CML66-reactive CD8+ T-cell clones were detected against an endogenously presented HLA-B*4403-restricted epitope (HDVDALLW). Neither CML66-specific antibody nor T-cell responses were detectable in peripheral blood before DLI. However, by 1 month after DLI, CD8+ T cells were present in peripheral blood and at 10-fold higher frequency in marrow. Subsequently, plasma antibody to CML66 developed in association with disease remission. Donor-derived CML66-reactive T cells were detected at low levels in vivo in marrow before DLI by ELISpot and by a nested PCR-based assay to detect clonotypic T-cell receptor sequences but not in blood of the patient pre-DLI nor of the graft donor.

Conclusions: CD4+ DLI results in rapid expansion of preexisting marrow-resident leukemia-specific donor CD8+ T cells, followed by a cascade of antigen-specific immune responses detectable in blood. Our single-antigen analysis thus shows that durable posttransplant tumor immunity is directed in part against nonpolymorphic overexpressed leukemia antigens that elicit coordinated cellular and humoral immunity.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology*
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / transplantation*
  • CD8-Positive T-Lymphocytes / immunology
  • Epitopes, T-Lymphocyte / immunology
  • HLA Antigens / immunology
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
  • Lymphocyte Activation / immunology
  • Lymphocyte Transfusion*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / therapy
  • Polymerase Chain Reaction
  • T-Lymphocytes / immunology


  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA Antigens
  • NUDCD1 protein, human