Anti-adenovirus type 5 cytotoxic T lymphocytes: immunodominant epitopes are encoded by the E1A gene

Routes, John M.; Bellgrau, Donald; McGrory, W.J.; Bautista, Diosdado S.; Graham, Frank L.; Cook, James L.

doi:10.1128/jvi.65.3.1450-1457.1991

Cited by 23 publications

(10 citation statements)

References 48 publications

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“…However, E1A expression during hAd2/5 infection of human cells fails to induce susceptibility to NK cell-mediated killing (46). hAd5 E1A CR1, CR2, and the second exon encode immunodominant CTL epitopes on adenovirus-infected rat cells (5,45,55). Therefore, E1A peptides presented on the surface of infected cells by MHC-I molecules target infected cells for elimination by CTL.…”

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confidence: 99%

The Role of Mouse Adenovirus Type 1 Early Region 1A in Acute and Persistent Infections in Mice

Smith

Brown

Spindler

1998

J Virol

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Mouse adenovirus type 1 (MAV-1) early region 1A (E1A) viral mutants were used to determine the importance of this region in pathogenesis and establishment of a persistent infection in the natural host. Lethal dose analysis with adult male Swiss outbred mice revealed a significant reduction in virulence for all of the E1A mutants. During acute infections with 105 PFU of virus, an E1A null mutant,pmE109, was found in the same organs (brain, spleen, and spinal cord) and the same cell types (endothelial cells and mononuclear cells in lymphoid tissue) as wild-type virus. Another null mutant,pmE112, was detected in the same organs but in lower numbers. However, when mice were given a lower dose, 1 PFU,pmE109 and pmE112 reached none of the target organs analyzed by 14 days postinfection (p.i.). The absence of E1A did not hinder the ability of MAV-1 to establish a persistent infection. Viral nucleic acid was detected by PCR amplification or in situ hybridization in the kidneys, brains, spleens, and prefemoral lymph nodes of mice infected with wild-type or mutant virus up to 55 weeks p.i. The brain, spleen, and lymph node are recognized sites of acute viral infection but are previously unrecognized sites for MAV-1 persistence. Evidence for the potential reactivation of persistent MAV-1 infections is also presented.

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confidence: 99%

The Role of Mouse Adenovirus Type 1 Early Region 1A in Acute and Persistent Infections in Mice

Smith

Brown

Spindler

1998

J Virol

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“…A second recent study (34) demonstrated that purified viral capsid proteins could stimulate proliferation of peripheral blood mononuclear cells in vitro, but the identity of the responding cells was not determined. In a series of investigations, Cook and colleagues have studied the role of NK cells in the killing of adenovirus-infected human cells and have shown that adenovirus sensitizes rodent, but not human, cells to NK cell killing (28)(29)(30)(31). These differences were ascribed to downregulation of major histocompatibility complex class I antigens on the cell surface of rodent, but not human, cells following virus infection (29).…”

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confidence: 99%

“…These studies cast doubt on the validity of using human adenovirus infection of mice as a model system. The major cytotoxic T-lymphocyte (CTL) response against adenovirus-infected rodent cells is directed against early viral proteins, either E1A (21,28,31) or E2A (18,22). This contrasts with preliminary findings on humans that show that viral capsid antigens are the targets of proliferative responses (10,34).…”

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Adenovirus-pulsed dendritic cells stimulate human virus-specific T-cell responses in vitro

Smith

Woodruff

Kitchingman

et al. 1996

J Virol

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Adenovirus infections cause significant morbidity and mortality in immunocompromised patients, yet little is known about the immune response to adenovirus infections. We established a system for the generation of a cytotoxic immune response to adenovirus in vitro. Cytotoxic T cells (CTLs) were derived from normal donors by using peripheral blood dendritic cells as antigen-presenting cells. The CTLs were found to contain a mixture of effector cells that recognized virus peptides in the context of both class I and class II antigens. Endogenous viral gene expression was not required to sensitize cells to lysis by adenovirus-specific CTLs. CTLs raised against subgroup C adenovirus type 5 can lyse cells infected with subgroup B adenovirus type 11, indicating that viruses of different subgroups have epitopes in common. This system holds promise for defining the human immune response to adenovirus, including characterization of the viral protein(s) against which the response is generated, and the identity of the effector cells. Such studies are in progress.

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“…In H-2Db mice, the second exon of Ad5 also codes for the sequences recognized as CTL target structures (Kast et al, 1989). In Fisher rats, however, results of differences of sensitivity to CTL killing of cells infected with Ad5 deletion mutants led to the hypothesis that the immunodominant epitopes map to the first E1A exon (Routes et al, 1991). Such difference in epitopes recognized by CTL of 2 allogeneic animal strains is not unique to the Ad system.…”

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confidence: 99%

Identification of functional domains of adenovirus tumor‐specific transplantation antigen in types 5 and 12 by viable viruses carrying chimeric E1A genes

Sawada

Rašková²,

Fujinaga

et al. 1994

Intl Journal of Cancer

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The adenovirus (Ad) E1A gene induces in immunized animals a strong tumor transplantation (TSTA) immunity against Ad tumors. Such immunity with group-A and group-C viruses is highly group-specific and no cross-protection is detected between serotypes 5 and 12. This fact was used to map the domains of the Ad5 and Ad12 E1A gene products, respectively, which control the TSTA. We constructed a library of 8 recombinant viruses (H5sub1101 through H5sub1108) which carry chimeric Ad5/Ad12 E1A genes in the background of Ad5. The chimeric genes are functional and these viruses are viable. Some of these constructs induce strong and highly specific tumor syngraft immunity in immunized rats. The viruses carrying the 5' terminus of the first E1A exon derived from Ad12 (viruses H5sub1101, H5sub1102 and H5sub1103) induce strong protection against Ad12 tumors irrespective of the rest of their E1A sequence. The viruses which carry the second exon of the Ad5 E1A gene (viruses H5sub1101, H5sub1102 and H5sub1106) protect against group-C tumors, regardless of the origin of the rest of their E1A gene. The 2 viruses that carry the 5' E1A terminus of the first exon of Ad12 and the second exon of Ad5 (H5sub1101 and H5sub1102) are thus effective in inducing immunity against Ad12 tumors as well as against Ad2 tumors. The viruses which carry the 5' terminus of the first exon derived from Ad5 and the second exon of Ad12 (H5sub1107 and H5sub 1108) fail to induce immunity against either tumor. Expression of only the truncated 5' terminus of the Ad12 E1A gene (viruses H5sub1104 and H5sub1105) is sufficient for induction of Ad12 TSTA. Our results provide direct and unequivocal in vivo evidence that TSTA activities of adenovirus groups A and C are controlled by different domains of their respective E1A genes. The Ad12 TSTA is a function of the 5' terminus of the first E1A exon, while the Ad5 TSTA is coded for by the 3' exon of its E1A gene.

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Anti-adenovirus type 5 cytotoxic T lymphocytes: immunodominant epitopes are encoded by the E1A gene

Cited by 23 publications

References 48 publications

The Role of Mouse Adenovirus Type 1 Early Region 1A in Acute and Persistent Infections in Mice

The Role of Mouse Adenovirus Type 1 Early Region 1A in Acute and Persistent Infections in Mice

Adenovirus-pulsed dendritic cells stimulate human virus-specific T-cell responses in vitro

Identification of functional domains of adenovirus tumor‐specific transplantation antigen in types 5 and 12 by viable viruses carrying chimeric E1A genes

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