scholarly journals Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and Magnitude of Tumor-Specific CD8+ T Cell Response

2018 ◽  
Vol 200 (10) ◽  
pp. 3464-3474 ◽  
Author(s):  
Hiep Khong ◽  
Annika Volmari ◽  
Meenu Sharma ◽  
Zhimin Dai ◽  
Chinonye S. Imo ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Cell Response ◽  
Peptide Vaccine ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Vaccine Formulation

scholarly journals Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections

2003 ◽  
Vol 198 (3) ◽  
pp. 399-410 ◽  
Author(s):  
Sherry R. Crowe ◽  
Stephen J. Turner ◽  
Shannon C. Miller ◽  
Alan D. Roberts ◽  
Rachel A. Rappolo ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Influenza Virus Infection ◽  
Cd8 T Cell ◽  
T Cell Response

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.

scholarly journals Murine Cytomegalovirus Interference with Antigen Presentation Has Little Effect on the Size or the Effector Memory Phenotype of the CD8 T Cell Response

2004 ◽  
Vol 172 (11) ◽  
pp. 6944-6953 ◽  
Author(s):  
Marielle C. Gold ◽  
Michael W. Munks ◽  
Markus Wagner ◽  
Christopher W. McMahon ◽  
Ann Kelly ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Murine Cytomegalovirus ◽  
Effector Memory ◽  
Memory Phenotype

scholarly journals Multiepitope CD8+ T cell response to a NY-ESO-1 peptide vaccine results in imprecise tumor targeting

2002 ◽  
Vol 110 (12) ◽  
pp. 1813-1822 ◽  
Author(s):  
Valérie Dutoit ◽  
Robert N. Taub ◽  
Kyriakos P. Papadopoulos ◽  
Susan Talbot ◽  
Mary-Louise Keohan ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Tumor Targeting ◽  
Peptide Vaccine ◽  
Cd8 T Cell ◽  
T Cell Response

Heparan sulfates targeting increases MHC class I- and MHC class II-restricted antigen presentation and CD8 + T-cell response

Vaccine ◽  
2016 ◽  
Vol 34 (27) ◽  
pp. 3093-3101 ◽  
Author(s):  
Delphine Knittel ◽  
Adeline Gadzinski ◽  
Stéphane Hua ◽  
Jordan Denizeau ◽  
Alexandra Savatier ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Cell Response ◽  
Cd8 T Cell ◽  
Class Ii ◽  
T Cell Response ◽  
Class I ◽  
Heparan Sulfates

scholarly journals 444 MHC-I skewing in mutant calreticulin-positive myeloproliferative neoplasms is countered by heteroclitic peptide cancer vaccination

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A470-A470
Author(s):  
Mathieu Gigoux ◽  
Roberta Zappasodi ◽  
Joseph Park ◽  
Stephane Pourpe ◽  
Arnab Ghosh ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Cancer Vaccines ◽  
Myeloproliferative Neoplasms ◽  
Peptide Vaccine ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Tumor Rejection ◽  
Cancer Center ◽  
Mhc I

BackgroundThe majority of JAK2V617F-negative myeloproliferative neoplasms (MPN) have disease-initiating frameshift mutations in calreticulin (CALR) resulting in a common novel C-terminal mutant fragment (CALRMUT), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALRMUT-specific T cells are rare in CALRMUT MPN patients, but the underlying reasons for this phenomenon are unknown.MethodsIn this study, we examine class-I major histocompatibility complex (MHC-I) allele frequency in CALRMUT MPN patients from two independent cohorts and observed that MHC-I alleles that present CALRMUT neoepitopes with high affinity are under-represented in CALRMUT MPN patients. We speculate that this is due to an increased chance of immune-mediated tumor rejection by individuals expressing one of these MHC-I alleles such that the disease never clinically manifests. As a consequence of this MHC-I allele restriction, we reasoned that CALRMUT MPN patients would not efficiently respond to cancer vaccines composed of the CALRMUT fragment, but could do so when immunized with a properly modified CALRMUT heteroclitic peptide vaccine approach.ResultsWe found that heteroclitic CALRMUT peptides specifically designed for CALRMUT MPN patient MHC-I alleles efficiently elicited a cross-reactive CD8+ T cell response in human PBMC samples otherwise unable to respond to the matched weakly immunogenic CALRMUT native peptides. We also modeled this effect in mice and observed that C57BL/6J mice, which are unable to mount an immune response to the human CALRMUT fragment, can mount a cross-reactive CD8+ T cell response against a CALRMUT-derived peptide upon heteroclitic peptide immunization and this was further amplified by combining the heteroclitic peptide vaccine with blockade of the immune checkpoint molecule PD-1.ConclusionsTogether, our data underscore the therapeutic potential of heteroclitic peptide-based cancer vaccines in CALRMUT MPN patients.Ethics ApprovalApproval was obtained for the use of patient-derived specimens and access to clinical data extracted from patient charts by the Institutional Review Boards at Memorial Sloan Kettering Cancer Center, the Dana-Farber Cancer Institute and the Massachusetts General Hospital, as well as by the Danish Regional Science Ethics Committee. Mouse experiments were performed in accordance with institutional guidelines under a protocol approved by the Memorial Sloan-Kettering Cancer Center Institutional Animal Care and Use Committee.

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