Lymphocytic Choriomeningitis Virus Infection Yields Overlapping CD4
            <sup>+</sup>
            and CD8
            <sup>+</sup>
            T-Cell Responses

Dow, C.; Oseroff, Carla; Peters, Bjoern; Nance-Sotelo, Courtney; Sidney, John; Buchmeier, Michael J.; Sette, Alessandro; Mothé, Bianca R.

doi:10.1128/jvi.00435-08

Cited by 34 publications

(57 citation statements)

References 54 publications

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“…Details of cattle MHC haplotypes, alleles, and nomenclature can be found at the website www.ebi.ac.uk/ipd/mhc/bola/. Animals were typed by PCR using sequence-specific primers (PCR-SSP), reference strand conformational analysis (RSCA) (1,6), or by indirect immunofluorescence (14,21).…”

Section: Viruses and Vaccinesmentioning

confidence: 99%

Induction of a Cross-Reactive CD8⁺T Cell Response following Foot-and-Mouth Disease Virus Vaccination

Guzman

Taylor

Charleston

et al. 2010

J Virol

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Section: Viruses and Vaccinesmentioning

confidence: 99%

Induction of a Cross-Reactive CD8⁺T Cell Response following Foot-and-Mouth Disease Virus Vaccination

Guzman

Taylor

Charleston

et al. 2010

J Virol

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“…Such help can be delivered to DCs by CD4 T cells (23), but also by other cell types (e.g., NKT cells) (37) or by nonspecific (e.g., TLR-triggered) help from cells of the innate immune system (38). Interestingly, some MHC class I-restricted epitopes are nested within CD4 T cell epitopes, suggesting that induction of these CD8 T cell responses is facilitated by a closely associated CD4 T cell helper function (33,34,(39)(40)(41). Little is known how CD4 T cells help particular dominant or subdominant CD8 T cell responses, and whether the (distant versus nested) position of the CD8 T cell epitope relative to a CD4 T cell epitope within a large Ag is critical for modulating the respective CD8 T cell specificities.…”

mentioning

confidence: 99%

The Immunodominant CD8 T Cell Response to the Human Cytomegalovirus Tegument Phosphoprotein pp65495–503 Epitope Critically Depends on CD4 T Cell Help in Vaccinated HLA-A*0201 Transgenic Mice

Reiser

Wieland

Plachter

et al. 2011

The Journal of Immunology

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Immunodominance hierarchies operating in immune responses to viral Ags limit the diversity of the elicited CD8 T cell responses. We evaluated in I-Ab+/A2-HHD-II and HLA-DR1+/A2-DR1 mice the HLA-A*0201–restricted, multispecific CD8 T cell responses to the human CMV tegument phosphoprotein pp65 (pp65) Ag. Vaccination of mice with pp65-encoding DNA elicited high IFN-γ+ CD8 T cell frequencies to the pp65495–503/(e6) epitope and low responses to the pp65320–328/(e3) and pp65522–530/(e8) epitopes. Abrogation of the e6-specific immunity efficiently enhanced e3- and e8-specific T cell responses by a pp65Δ501–503 DNA vaccine. The immunodominant e6-specific (but not the e3- and e8-specific) CD8 T cell response critically depends on CD4 T cell help. Injection of monospecific DNA- or peptide-based vaccines encoding the e3 or e8 (but not the e6) epitope into mice elicited CD8 T cells. Codelivering the antigenic peptides with different heterologous CD4 T cell helper epitopes enhanced e6-specific (but not e3- or e8-specific) CD8 T cell responses. Similarly, homologous CD4 T cell help, located within an overlapping (nested) pp65487–503 domain, facilitated induction of e6-specific CD8 T cell responses by peptide-based vaccination. The position of the e6 epitope within this nested domain is not critical to induce the immunodominant, e6-specific CD8 T cell response to the pp65 Ag. Distant CD4 T cell epitope(s) can thus provide efficient help for establishing pp65-e6 immunodominance in vaccinated mice. These results have practical implications for the design of new T cell-stimulating vaccines.

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“…This study demonstrated a second instance of a CD4 ϩ T cell epitope containing a nested CD8 ϩ T cell epitope (GPC [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] and GPC [33][34][35][36][37][38][39][40][41] , respectively). The overlap of the CD4 ϩ and CD8 ϩ T cell immune responses might be related to the immunodominance of particular viral regions and might be influenced by proteasomal processing, MHC binding affinity, and/or TCR repertoires (31). Taken together, these studies also demonstrated that the LCMV-specific CD4 ϩ T cell response is more complex than previously appreciated.…”

Section: Identification Of Cd8 ؉ and Cd4 ؉ T Cell-mediated Immune Resmentioning

confidence: 99%

Coverage of Related Pathogenic Species by Multivalent and Cross-Protective Vaccine Design: Arenaviruses as a Model System

Botten

Sidney

Mothé

et al. 2010

Microbiol Mol Biol Rev

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SUMMARY The arenaviruses are a family of negative-sense RNA viruses that cause severe human disease ranging from aseptic meningitis to hemorrhagic fever syndromes. There are currently no FDA-approved vaccines for the prevention of arenavirus disease, and therapeutic treatment is limited to the use of ribavirin and/or immune plasma for a subset of the pathogenic arenaviruses. The considerable genetic variability observed among the seven arenaviruses that are pathogenic for humans illustrates one of the major challenges for vaccine development today, namely, to overcome pathogen heterogeneity. Over the past 5 years, our group has tested several strategies to overcome pathogen heterogeneity, utilizing the pathogenic arenaviruses as a model system. Because T cells play a prominent role in protective immunity following arenavirus infection, we specifically focused on the development of human vaccines that would induce multivalent and cross-protective cell-mediated immune responses. To facilitate our vaccine development and testing, we conducted large-scale major histocompatibility complex (MHC) class I and class II epitope discovery on murine, nonhuman primate, and human backgrounds for each of the pathogenic arenaviruses, including the identification of protective HLA-restricted epitopes. Finally, using the murine model of lymphocytic choriomeningitis virus infection, we studied the phenotypic characteristics associated with immunodominant and protective T cell epitopes. This review summarizes the findings from our studies and discusses their application to future vaccine design.

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Lymphocytic Choriomeningitis Virus Infection Yields Overlapping CD4 ⁺ and CD8 ⁺ T-Cell Responses

Cited by 34 publications

References 54 publications

Induction of a Cross-Reactive CD8⁺T Cell Response following Foot-and-Mouth Disease Virus Vaccination

Induction of a Cross-Reactive CD8⁺T Cell Response following Foot-and-Mouth Disease Virus Vaccination

The Immunodominant CD8 T Cell Response to the Human Cytomegalovirus Tegument Phosphoprotein pp65495–503 Epitope Critically Depends on CD4 T Cell Help in Vaccinated HLA-A*0201 Transgenic Mice

Coverage of Related Pathogenic Species by Multivalent and Cross-Protective Vaccine Design: Arenaviruses as a Model System

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Lymphocytic Choriomeningitis Virus Infection Yields Overlapping CD4 + and CD8 + T-Cell Responses

Cited by 34 publications

References 54 publications

Induction of a Cross-Reactive CD8+T Cell Response following Foot-and-Mouth Disease Virus Vaccination

Induction of a Cross-Reactive CD8+T Cell Response following Foot-and-Mouth Disease Virus Vaccination

The Immunodominant CD8 T Cell Response to the Human Cytomegalovirus Tegument Phosphoprotein pp65495–503 Epitope Critically Depends on CD4 T Cell Help in Vaccinated HLA-A*0201 Transgenic Mice

Coverage of Related Pathogenic Species by Multivalent and Cross-Protective Vaccine Design: Arenaviruses as a Model System

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Product

Resources

About

Lymphocytic Choriomeningitis Virus Infection Yields Overlapping CD4 ⁺ and CD8 ⁺ T-Cell Responses

Induction of a Cross-Reactive CD8⁺T Cell Response following Foot-and-Mouth Disease Virus Vaccination

Induction of a Cross-Reactive CD8⁺T Cell Response following Foot-and-Mouth Disease Virus Vaccination