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Evaluation of cytomegalovirus-specific cytotoxic T-lymphocytes in patients with the HLA-A*02 or HLA-A*24 phenotype undergoing hematopoietic stem cell transplantation

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Summary:

Cytomegalovirus-specific cytotoxic T-lymphocytes (CMV-CTL) are essential for the control of CMV reactivation. To monitor the quantity and function of CMV-CTL after hematopoietic stem cell transplantation (HSCT), two CMV epitopes that bind to HLA-A*0201 NLVPMVATV (A*02NLV) and HLA-A*2402 QYDPVAALF (A*24QYD) were evaluated for their immunological potential. Samples from patients with the HLA-A*02 or HLA-A*24 serotype were analyzed by tetramer, intracellular cytokine staining and enzyme-linked immunospot (ELISPOT) assay. There were significantly more A*02NLV-specific CMV-CTL than A*24QYD (23 × 106 vs 0.4 × 106/l). The frequency of IFN-γ-producing cells was also higher upon stimulation with A*02NLV than with A*24QYD (2.5 vs 0.1%/CD8). Furthermore, the magnitude of CMV-CTL expansion was two- to 50-fold when cells were cultured with A*02NLV, while only an insignificant increase was observed in culture with A*24QYD. Although the number of A*24QYD-specific CMV-CTL was very low in most of the HLA-A*24 patients, the incidence of CMV reactivation did not differ between those with HLA-A*02 and HLA-A*24 serotype alone. These results suggest that an epitope other than A*24QYD plays a major role in patients with HLA-A*24. Our study also showed that A*02NLV may be a useful epitope for monitoring CMV-CTL not only in patients with HLA-A*0201 but also in those with the A*0206 genotype.

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Authors and Affiliations

  1. Division of Hematology and Stem Cell Transplantation, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan

    Y Morita, M Hosokawa, Y Takaue & Y Heike

  2. Department of Hematology and Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

    Y Morita & O Miura

  3. SRL Inc., Tokyo, Japan

    M Ebisawa & T Sugita

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  1. Y Morita
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  2. M Hosokawa
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  3. M Ebisawa
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  4. T Sugita
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  5. O Miura
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  6. Y Takaue
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  7. Y Heike
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Correspondence to Y Takaue.

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Morita, Y., Hosokawa, M., Ebisawa, M. et al. Evaluation of cytomegalovirus-specific cytotoxic T-lymphocytes in patients with the HLA-A*02 or HLA-A*24 phenotype undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 36, 803–811 (2005). https://doi.org/10.1038/sj.bmt.1705133

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  • DOI: https://doi.org/10.1038/sj.bmt.1705133

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