scholarly journals Structural basis for ineffective T-cell responses to MHC anchor residue-improved “heteroclitic” peptides

2014 ◽  
Vol 45 (2) ◽  
pp. 584-591 ◽  
Author(s):  
Florian Madura ◽  
Pierre J. Rizkallah ◽  
Christopher J. Holland ◽  
Anna Fuller ◽  
Anna Bulek ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Structural Basis ◽  
Anchor Residue ◽  
Cell Responses ◽  
Heteroclitic Peptides

scholarly journals Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses

2011 ◽  
Vol 108 (23) ◽  
pp. 9536-9541 ◽  
Author(s):  
E. B. Day ◽  
C. Guillonneau ◽  
S. Gras ◽  
N. L. La Gruta ◽  
D. A. A. Vignali ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Structural Basis ◽  
Cell Responses

Heteroclitic peptides enhance human immunodeficiency virus-specific CD8+ T cell responses

Vaccine ◽  
2012 ◽  
Vol 30 (49) ◽  
pp. 6997-7004 ◽  
Author(s):  
Krista H. Gladney ◽  
Julia Pohling ◽  
Natasha A. Hollett ◽  
Katrin Zipperlen ◽  
Maureen E. Gallant ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Heteroclitic Peptides

scholarly journals P03.01 High immunogenic VLP-based vaccines elicit new T cell specificities against melanoma neoantigens in mice

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A13.1-A13
Author(s):  
C Aguilar-Gurrieri ◽  
A Barajas ◽  
A Pons-Grifols ◽  
I Varela ◽  
P Amengual-Rigo ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Therapeutic Vaccine ◽  
T Cell Responses ◽  
Advisory Board ◽  
Tumor Control ◽  
Vaccine Platform ◽  
Anchor Residue ◽  
Synonymous Mutations ◽  
Cell Responses

BackgroundNeoantigens’ (neoAg) identification, which determines T-cell responses against tumors, has fostered the development of personalized vaccines with promising results. While the ranking of the most immunogenic neoAg can be addressed using predictive techniques, their formulation as vaccines needs to be improved. To maximize their therapeutic potential, optimal neoAg-based vaccines should be manufactured in a superb delivery platform that enhances robust new immune responses, able to bypass thymic tolerance and the humoral immunosuppressive microenvironment. These novel T cell responses generated at the periphery will not be exhausted, opposite to TILs. We aim to develop a highly immunogenic vaccine platform, based on engineered HIV-derived Virus-Like Particles (VLP) expressing approximately 2500 copies of each selected neoAg. We tested different neoAgs loaded VLPs (neoVLP) in a melanoma mouse model to evaluate their capability to generate new immunogenic specificities.Material and MethodsSpecific non-synonymous mutations from B16F10 cells were identified, selected and used to generate a list of prioritized peptides. NeoAgs were classified as: Tier1, acquiring a mutation that creates an anchor residue to the MHC-I, not present in the WT peptide; Tier2, acquiring a mutation in a position that largely impacts contact with the TCR respect to WT; and Tier3, acquiring a mutation in the TCR contact region but inducing a less drastic change than in Tier2. Frame shift (FS) mutations, expected to be highly immunogenic, were also included.Thirteen to fifteen selected neoAgs from each group were loaded on highly immunogenic neoVLPs. Their immunogenicity was evaluated in C57bl/6 mice by immunization with a neoVLP-coding plasmid DNA (prime) and purified neoVLPs as soluble particles (boost). Splenocytes were used to evaluate neoAg-specific T cell responses.ResultsWe have successfully generated and purified neoVLPs, exposing neoAgs from all groups by transient transfection of Expi293 cells. Protein integrity and VLP morphology were confirmed by western blot and cryo-EM. When used for immunization assays, neoVLPs, containing neoAgs from Tier2, Tier3 and FS groups, were capable of generating humoral responses against viral proteins and T cell responses against neoAgs present in the neoVLP. B16F10 inoculated animals, but not vaccinated, did not develop detectable T cell responses against neoAgs present in any tested neoVLP, suggesting that the vaccination with neoVLPs promoted new specificities against selected neoAgs that might contribute to tumor control and eradication.ConclusionOur data show that the neoVLPs promote the generation of new antitumor-specific immune responses against selected neoepitopes, suggesting that neoVLPs vaccination could be an alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy.Disclosure InformationC. Aguilar-Gurrieri: None. A. Barajas: None. A. Pons-Grifols: None. I. Varela: None. P. Amengual-Rigo: None. R. Farriol: None. M. Vazquez: None. R. Lepore: None. C. Anjos-Souza: None. J. Blanco-Heredia: None. L. de Mattos-Arruda: None. V. Guallar: None. A. Valencia: None. B. Clotet: F. Consultant/Advisory Board; Significant; Albajuna Therapeutics. J. Carrillo: Other; Significant; Albajuna Therapeutics. J. Blanco: F. Consultant/Advisory Board; Significant; Albajuna Therapeutics.

scholarly journals HLA class I genotypes customize vaccination strategies in immune simulation to combat COVID-19

2020 ◽  
Author(s):  
Shouxiong Huang ◽  
Ming Tan
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Vaccination Strategy ◽  
T Cell Responses ◽  
Hla Class I ◽  
Class I ◽  
Human Populations ◽  
Anchor Residue ◽  
Cell Responses

AbstractMemory CD8+ T cells are associated with a better outcome in Coronavirus Disease 2019 (COVID-19) and recognized as promising vaccine targets against viral infections. This study determined the efficacy of population-dominant and infection-relevant human leukocyte antigens (HLA) class I proteins to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides through calculating binding affinities and simulating CD8+ T cell responses. As a result, HLA class I proteins distinguished or shared various viral peptides derived from viruses. HLA class I supertypes clustered viral peptides through recognizing anchor and preferred residues. SARS-CoV-2 peptides overlapped significantly with SARS but minimally with common human coronaviruses. Immune simulation of CD8+ T cell activation using predicted SARS-CoV-2 peptide antigens depended on high-affinity peptide binding, anchor residue interaction, and synergistic presentation of HLA class I proteins in individuals. Results demonstrated that multi-epitope vaccination, employing a strong binding affinity, viral adjuvants, and heterozygous HLA class I genes, induced potent immune responses. Therefore, optimal CD8+ T cell responses can be achieved and customized contingent on HLA class I genotypes in human populations, supporting a precise vaccination strategy to combat COVID-19.

scholarly journals Noncompetitive Expansion of Cytotoxic T Lymphocytes Specific for Different Antigens during Bacterial Infection

1999 ◽  
Vol 67 (3) ◽  
pp. 1303-1309 ◽  
Author(s):  
Sujata Vijh ◽  
Ingrid M. Pilip ◽  
Eric G. Pamer
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Wild Type ◽  
Antigen Specificity ◽  
Anchor Residue ◽  
Cell Responses ◽  
T Cell Priming ◽  
Naive T Lymphocytes

ABSTRACT Listeria monocytogenes is an intracellular bacterium that elicits complex cytotoxic T-lymphocyte (CTL) responses in infected mice. The responses of CTL populations that differ in antigen specificity range in magnitude from large, dominant responses to small, subdominant responses. To test the hypothesis that dominant T-cell responses inhibit subdominant responses, we eliminated the two dominant epitopes of L. monocytogenes by anchor residue mutagenesis and measured the T-cell responses to the remaining subdominant epitopes. Surprisingly, the loss of dominant T-cell responses did not enhance subdominant responses. While mice immunized with bacteria lacking dominant epitopes developed L. monocytogenes-specific immunity, their ability to respond to dominant epitopes upon rechallenge with wild-type bacteria was markedly diminished. Recall responses in mice immunized with wild-type or epitope-deficient L. monocytogenes showed that antigen presentation during recall infection is sufficient for activating memory cells yet insufficient for optimal priming of naive T lymphocytes. Our findings suggest that T-cell priming to different epitopes during L. monocytogenes infection is not competitive. Rather, T-cell populations specific for different antigens but the same pathogen expand independently.

Sign in / Sign up

Export Citation Format

Share Document