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

76 Citations (Scopus)

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 - Jan 15 2004
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Hematology

Cite this

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, 103(2), 630-638. https://doi.org/10.1182/blood-2003-03-0824