Identification of Vaccinia CD8+ T-Cell Epitopes Conserved among Vaccinia and Variola Viruses Restricted by Common MHC Class I Molecules, HLA-A2 or HLA-B7

Terajima, Masanori; Cruz, John; Leporati, Anita M.; Demkowicz, Walter E.; Kennedy, Jennifer; Ennis, Francis A.

doi:10.1016/j.humimm.2005.12.004

Cited by 35 publications

(36 citation statements)

References 32 publications

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“…This level of completeness is unusual for T cell studies in humans or mice. In some previous studies of CD8 responses to vaccinia, the summation of peptide-specific responses actually exceeded the response to whole virus, in at least some donors (53,62,63). We titered the whole virus preparation, and used it at the concentration giving maximal CD4 IFN-␥ responses (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Jing¹,

Chong

Byrd³

et al. 2007

The Journal of Immunology

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Vaccination with replication-competent vaccinia protects against heterologous orthopoxvirus challenge. CD4 T cells have essential roles helping functionally important Ab and CD8 antiviral responses, and contribute to the durability of vaccinia-specific memory. Little is known about the specificity, diversity, or dominance hierarchy of orthopoxvirus-specific CD4 T cell responses. We interrogated vaccinia-reactive CD4 in vitro T cell lines with vaccinia protein fragments expressed from an unbiased genomic library, and also with a panel of membrane proteins. CD4 T cells from three primary vaccinees reacted with 44 separate antigenic regions in 35 vaccinia proteins, recognizing 8 to 20 proteins per person. The integrated responses to the Ags that we defined accounted for 49 to 81% of the CD4 reactivity to whole vaccinia Ag. Individual dominant Ags drove up to 30% of the total response. The gene F11L-encoded protein was immunodominant in two of three subjects and is fragmented in a replication-incompetent vaccine candidate. The presence of protein in virions was strongly associated with CD4 antigenicity. These findings are consistent with models in which exogenous Ag drives CD4 immunodominance, and provides tools to investigate the relationship between Ab and CD4 T cell specificity for complex pathogens.

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Section: Discussionmentioning

confidence: 99%

“…We compared CD4 Ags to those that drive human or murine HLA-transgenic CD8 ϩ responses (26,53,58,62,(73)(74)(75)(76)(77). Overall 16 ORFs (A3L, A10L, A33R, A34R, A48R, A50R, B19R, C3L, C10L, D5R, E3L, G7L, H3L, I3L, J6R, and O1L) are both CD4 and CD8 Ags.…”

Section: Discussionmentioning

confidence: 99%

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Jing¹,

Chong

Byrd³

et al. 2007

The Journal of Immunology

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“…We are currently investigating the mechanisms involved in this effect, by analyzing whether cotransfer of T cells specific for dominant epitopes can directly inhibit T cell responses to subdominant epitopes, as well as studying the specificity of this effect using irrelevant epitopes as immunogens. Furthermore, because it has been shown that both the site and route of administration as well as the coexpression of other MHC molecules within the infected host can influence the actual repertoire of epitopes recognized (4,8,12,13,58), these variables need to be fully considered. As mentioned above, it is also possible that an inordinately high binding affinity might lead to exhaustion or tolerization of the T cells recognizing subdominant epitopes.…”

Section: Discussionmentioning

confidence: 99%

“…It must be emphasized that this number is likely an underestimation, as additional proteins targeted by CD8 ϩ T cell responses may yet be identified (Supplemental Table IA). 4 Of the Ͼ115,000 possible 9-and 10-mer peptides encoded in the entire VACV genome, these 102 antigenic proteins encode a total of 67,150 peptides. The studies described below are limited to these 102 proteins.…”

Section: Approximately One-half Of Vacv-derived Proteins Are Potentiamentioning

confidence: 99%

“…Based on our database of A*0201 binding affinities, it is estimated that ϳ95% of the peptides with the capacity to bind A*0201 with affinities Ͻ100 nM are motif positive. Fewer than 0.2% of peptides without this 4 The on-line version of this article contains supplemental material. To exclude protein expression as a possible factor in our analysis of epitope recognition, we have restricted our analysis to VACV proteins that are known to contain epitopes that induce CD8 ϩ T cell responses after infection.…”

Section: Frequency Of A*0201 Binders In Vacv Proteinsmentioning

confidence: 99%

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A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection

Assarsson

Sidney

Oseroff

et al. 2007

The Journal of Immunology

173

197

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Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022

Wang

Shang

Weng

et al. 2022

Journal of Medical Virology

127

126

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Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several nonendemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV‐2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV‐2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV‐2022 strains, including 24 nonsynonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that 10 proteins in the MPXV are more prone to mutation, including D2L‐like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L‐like, OPG153, OPG188, and OPG210 proteins. In the MPXV‐2022 strains, four and three nucleotide substitutions are observed in OPG105 and OPG210, respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.

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Identification of Vaccinia CD8+ T-Cell Epitopes Conserved among Vaccinia and Variola Viruses Restricted by Common MHC Class I Molecules, HLA-A2 or HLA-B7

Cited by 35 publications

References 32 publications

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection

Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022

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