Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles

Eisei Kondo, Yoshiki Akatsuka, Kiyotaka Kuzushima, Kunio Tsujimura, Shoji Asakura, Kohei Tajima, Yoshitoyo Kagami, Yoshihisa Kodera, Mitsune Tanimoto, Yasuo Morishima, Toshitada Takahashi

Research output: Contribution to journalArticle

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Abstract

Cytomegalovirus (CMV)-specific T-cell immunity plays an important role in protection from CMV disease in immunocompromised patients. Identification of cytotoxic T-lymphocyte (CTL) epitopes is essential for monitoring T-cell immunity and also for immunotherapy. In this and previous studies, CMV-pp65-specific CTL lines were successfully generated from all of 11 CMV-seropositive healthy donors, using pp65-transduced CD40-activated B (CD40-B) cells as antigen-presenting cells. By use of enzyme-linked immunospot (ELISPOT) assays, individual CTL epitopes could be mapped with truncated forms of the pp65 gene. For human leukocyte antigen (HLA) alleles with a known binding motif, CTL epitopes within the defined regions were predicted by computer algorithm. For HLA alleles without a known binding motif (HLA-Cw*0801, -Cw*1202, and -Cw*1502), the epitopes were alternatively Identified by step-by-step truncations of the pp65 gene. Through this study, a total of 14 novel CTL epitopes of CMV-pp65 were identified. Interestingly, 3 peptides were found to be presented by 2 different HLA class I alleles or subtypes. Moreover, use of CD40-B cells pulsed with a mixture of synthetic peptides led to generation of pp65-specific CTL lines from some of seronegative donors. The study thus demonstrated an efficient strategy for identifying CTL epitopes presented by a variety of HLA alleles.

Original languageEnglish
Pages (from-to)630-638
Number of pages9
JournalBlood
Volume103
Issue number2
DOIs
Publication statusPublished - 15-01-2004

Fingerprint

T-Lymphocyte Epitopes
Cytotoxic T-Lymphocytes
HLA Antigens
Cytomegalovirus
T-cells
Alleles
Genes
Cells
Peptides
Immunity
B-Lymphocytes
T-Lymphocytes
Enzyme-Linked Immunospot Assay
Epitopes
Assays
Immunocompromised Host
Antigen-Presenting Cells
Immunotherapy
Monitoring
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Kondo, E., Akatsuka, Y., Kuzushima, K., Tsujimura, K., Asakura, S., Tajima, K., ... Takahashi, T. (2004). Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles. Blood, 103(2), 630-638. https://doi.org/10.1182/blood-2003-03-0824
Kondo, Eisei ; Akatsuka, Yoshiki ; Kuzushima, Kiyotaka ; Tsujimura, Kunio ; Asakura, Shoji ; Tajima, Kohei ; Kagami, Yoshitoyo ; Kodera, Yoshihisa ; Tanimoto, Mitsune ; Morishima, Yasuo ; Takahashi, Toshitada. / Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles. In: Blood. 2004 ; Vol. 103, No. 2. pp. 630-638.
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author = "Eisei Kondo and Yoshiki Akatsuka and Kiyotaka Kuzushima and Kunio Tsujimura and Shoji Asakura and Kohei Tajima and Yoshitoyo Kagami and Yoshihisa Kodera and Mitsune Tanimoto and Yasuo Morishima and Toshitada Takahashi",
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Kondo, E, Akatsuka, Y, Kuzushima, K, Tsujimura, K, Asakura, S, Tajima, K, Kagami, Y, Kodera, Y, Tanimoto, M, Morishima, Y & Takahashi, T 2004, 'Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles', Blood, vol. 103, no. 2, pp. 630-638. https://doi.org/10.1182/blood-2003-03-0824

Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles. / Kondo, Eisei; Akatsuka, Yoshiki; Kuzushima, Kiyotaka; Tsujimura, Kunio; Asakura, Shoji; Tajima, Kohei; Kagami, Yoshitoyo; Kodera, Yoshihisa; Tanimoto, Mitsune; Morishima, Yasuo; Takahashi, Toshitada.

In: Blood, Vol. 103, No. 2, 15.01.2004, p. 630-638.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles

AU - Kondo, Eisei

AU - Akatsuka, Yoshiki

AU - Kuzushima, Kiyotaka

AU - Tsujimura, Kunio

AU - Asakura, Shoji

AU - Tajima, Kohei

AU - Kagami, Yoshitoyo

AU - Kodera, Yoshihisa

AU - Tanimoto, Mitsune

AU - Morishima, Yasuo

AU - Takahashi, Toshitada

PY - 2004/1/15

Y1 - 2004/1/15

N2 - Cytomegalovirus (CMV)-specific T-cell immunity plays an important role in protection from CMV disease in immunocompromised patients. Identification of cytotoxic T-lymphocyte (CTL) epitopes is essential for monitoring T-cell immunity and also for immunotherapy. In this and previous studies, CMV-pp65-specific CTL lines were successfully generated from all of 11 CMV-seropositive healthy donors, using pp65-transduced CD40-activated B (CD40-B) cells as antigen-presenting cells. By use of enzyme-linked immunospot (ELISPOT) assays, individual CTL epitopes could be mapped with truncated forms of the pp65 gene. For human leukocyte antigen (HLA) alleles with a known binding motif, CTL epitopes within the defined regions were predicted by computer algorithm. For HLA alleles without a known binding motif (HLA-Cw*0801, -Cw*1202, and -Cw*1502), the epitopes were alternatively Identified by step-by-step truncations of the pp65 gene. Through this study, a total of 14 novel CTL epitopes of CMV-pp65 were identified. Interestingly, 3 peptides were found to be presented by 2 different HLA class I alleles or subtypes. Moreover, use of CD40-B cells pulsed with a mixture of synthetic peptides led to generation of pp65-specific CTL lines from some of seronegative donors. The study thus demonstrated an efficient strategy for identifying CTL epitopes presented by a variety of HLA alleles.

AB - Cytomegalovirus (CMV)-specific T-cell immunity plays an important role in protection from CMV disease in immunocompromised patients. Identification of cytotoxic T-lymphocyte (CTL) epitopes is essential for monitoring T-cell immunity and also for immunotherapy. In this and previous studies, CMV-pp65-specific CTL lines were successfully generated from all of 11 CMV-seropositive healthy donors, using pp65-transduced CD40-activated B (CD40-B) cells as antigen-presenting cells. By use of enzyme-linked immunospot (ELISPOT) assays, individual CTL epitopes could be mapped with truncated forms of the pp65 gene. For human leukocyte antigen (HLA) alleles with a known binding motif, CTL epitopes within the defined regions were predicted by computer algorithm. For HLA alleles without a known binding motif (HLA-Cw*0801, -Cw*1202, and -Cw*1502), the epitopes were alternatively Identified by step-by-step truncations of the pp65 gene. Through this study, a total of 14 novel CTL epitopes of CMV-pp65 were identified. Interestingly, 3 peptides were found to be presented by 2 different HLA class I alleles or subtypes. Moreover, use of CD40-B cells pulsed with a mixture of synthetic peptides led to generation of pp65-specific CTL lines from some of seronegative donors. The study thus demonstrated an efficient strategy for identifying CTL epitopes presented by a variety of HLA alleles.

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Kondo E, Akatsuka Y, Kuzushima K, Tsujimura K, Asakura S, Tajima K et al. Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles. Blood. 2004 Jan 15;103(2):630-638. https://doi.org/10.1182/blood-2003-03-0824