T cell epitope mapping of JC polyoma virus-encoded proteome reveals reduced T cell responses in HLA-DRB1*04:01+ donors.
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T cell epitope mapping of JC polyoma virus-encoded proteome reveals reduced T cell responses in HLA-DRB1*04:01+ donors. / Jelcic, Ilijas; Aly, Lilian; Binder, Thomas; Jelcic, Ivan; Bofill-Mas, Sílvia; Planas, Raquel; Demina, Victoria; Eiermann, Thomas; Weber, Thomas; Girones, Rosina; Sospedra, Mireia; Martin, Roland.
In: J VIROL, Vol. 87, No. 6, 6, 2013, p. 3393-3408.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - T cell epitope mapping of JC polyoma virus-encoded proteome reveals reduced T cell responses in HLA-DRB1*04:01+ donors.
AU - Jelcic, Ilijas
AU - Aly, Lilian
AU - Binder, Thomas
AU - Jelcic, Ivan
AU - Bofill-Mas, Sílvia
AU - Planas, Raquel
AU - Demina, Victoria
AU - Eiermann, Thomas
AU - Weber, Thomas
AU - Girones, Rosina
AU - Sospedra, Mireia
AU - Martin, Roland
PY - 2013
Y1 - 2013
N2 - JC polyomavirus (JCV) infection is highly prevalent and usually kept in a persistent state without clinical signs and symptoms. It is only during immunocompromise and especially impaired CD4(+) T cell function in the brain, as seen in AIDS patients or natalizumab-treated multiple sclerosis patients, that JCV may cause progressive multifocal leukoencephalopathy (PML), an often life-threatening brain disease. Since CD4(+) T cells likely play an important role in controlling JCV infection, we here describe the T cell response to JCV in a group of predominantly HLA-DR-heterozygotic healthy donors (HD) by using a series of overlapping 15-mer peptides spanning all JCV-encoded open reading frames. We identified immunodominant epitopes and compared T cell responses with anti-JCV VP1 antibody production and with the presence of urinary viral shedding. We observed positive JCV-specific T cell responses in 28.6% to 77.6%, humoral immune response in 42.6% to 89.4%, and urinary viral shedding in 36.4% to 45.5% of HD depending on the threshold. Four immunodominant peptides were mapped, and at least one immunogenic peptide per HLA-DRB1 allele was detected in DRB1*01(+), DRB1*07(+), DRB1*11(+), DRB1*13(+), DRB1*15(+), and DRB1*03(+) individuals. We show for the first time that JCV-specific T cell responses may be directed not only against JCV VP1 and large T antigen but also against all other JCV-encoded proteins. Heterozygotic DRB1*04:01(+) individuals showed very low T cell responses to JCV together with normal anti-VP1 antibody levels and no urinary viral shedding, indicating a dominant-negative effect of this allele on global JCV-directed T cell responses. Our data are potentially relevant for the development of vaccines against JCV.
AB - JC polyomavirus (JCV) infection is highly prevalent and usually kept in a persistent state without clinical signs and symptoms. It is only during immunocompromise and especially impaired CD4(+) T cell function in the brain, as seen in AIDS patients or natalizumab-treated multiple sclerosis patients, that JCV may cause progressive multifocal leukoencephalopathy (PML), an often life-threatening brain disease. Since CD4(+) T cells likely play an important role in controlling JCV infection, we here describe the T cell response to JCV in a group of predominantly HLA-DR-heterozygotic healthy donors (HD) by using a series of overlapping 15-mer peptides spanning all JCV-encoded open reading frames. We identified immunodominant epitopes and compared T cell responses with anti-JCV VP1 antibody production and with the presence of urinary viral shedding. We observed positive JCV-specific T cell responses in 28.6% to 77.6%, humoral immune response in 42.6% to 89.4%, and urinary viral shedding in 36.4% to 45.5% of HD depending on the threshold. Four immunodominant peptides were mapped, and at least one immunogenic peptide per HLA-DRB1 allele was detected in DRB1*01(+), DRB1*07(+), DRB1*11(+), DRB1*13(+), DRB1*15(+), and DRB1*03(+) individuals. We show for the first time that JCV-specific T cell responses may be directed not only against JCV VP1 and large T antigen but also against all other JCV-encoded proteins. Heterozygotic DRB1*04:01(+) individuals showed very low T cell responses to JCV together with normal anti-VP1 antibody levels and no urinary viral shedding, indicating a dominant-negative effect of this allele on global JCV-directed T cell responses. Our data are potentially relevant for the development of vaccines against JCV.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - JC Virus/immunology
KW - Epitope Mapping
KW - T-Lymphocytes/immunology
KW - Antibodies, Viral/blood
KW - Epitopes, T-Lymphocyte/analysis
KW - HLA-DRB1 Chains/genetics/immunology
KW - Immunodominant Epitopes/analysis
KW - Proteome/immunology
KW - Urine/virology
KW - Virus Shedding
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - JC Virus/immunology
KW - Epitope Mapping
KW - T-Lymphocytes/immunology
KW - Antibodies, Viral/blood
KW - Epitopes, T-Lymphocyte/analysis
KW - HLA-DRB1 Chains/genetics/immunology
KW - Immunodominant Epitopes/analysis
KW - Proteome/immunology
KW - Urine/virology
KW - Virus Shedding
M3 - SCORING: Journal article
VL - 87
SP - 3393
EP - 3408
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 6
M1 - 6
ER -
