Identification of GP100-derived, melanoma-specific cytotoxic T-lymphocyte epitopes restricted by HLA-A3 supertype molecules by primaryin vitro immunization with peptide-pulsed dendritic cells

Kawashima, Ichiro; Tsai, Van; Southwood, Scott; Takesako, Kazutoh; Celis, Esteban; Sette, Alessandro

doi:10.1002/(sici)1097-0215(19981109)78:4<518::aid-ijc20>3.0.co;2-0

“…One control peptide (ctl3) was also not detected by MS after peptide pulsing. This peptide's high positive charge probably resulted in limited capacity factor (k') and irreproducible MS detection [72]. Overall, the high detection rate of TSAs (90% at t=0h) and their abundance comparable to immunogenic viral peptides after moDCs' pulsing evocate a good immunogenic potential.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens

Hesnard,

Thériault,

Cahuzac

et al. 2024

Preprint

0

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

show abstract

“…One control peptide (ctl3) was also not detected by MS after peptide pulsing. This peptide’s high positive charge probably resulted in a limited capacity factor (k’) and irreproducible MS detection [ 72 ]. Overall, the high detection rate of TSAs (90% at t = 0 h) and their abundance comparable to immunogenic viral peptides after moDC pulsing evocate a good immunogenic potential.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens

Hesnard,

Thériault,

Cahuzac

et al. 2024

Current Oncology

0

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

show abstract

“…The discovery of HLA supertypes led to the description of common binding motifs within peptides that bind a supertype and are collectively called ’supermotifs‘ [ 68 , 70 ]. Most importantly, peptide ligands predicted based on algorithms that have taken into account supermotifs have led to the discovery of numerous virus‐derived CD8 + T cell epitopes [ 76 , 77 , 78 , 79 , 80 ]. A recent in‐depth study of naturally processed immunopeptidomes of 95 distinct HLA‐A, HLA‐B and HLA‐C molecules by high‐resolution mass spectrometry has further refined supertypes based on HLA‐I binding submotifs.…”

Section: Essential Structural Basis Of Antigen Presentationmentioning

confidence: 99%

Know thy immune self and non‐self: Proteomics informs on the expanse of self and non‐self, and how and where they arise

Joyce

¹

,

Ternette

²

2021

View full text Add to dashboard Cite

T cells play an important role in the adaptive immune response to a variety of infections and cancers. Initiation of a T cell mediated immune response requires antigen recognition in a process termed MHC (Major Histocompatibility Complex) restriction. A T cell antigen is a composite structure made up of a peptide fragment bound within the antigen-binding groove of an MHC-encoded class I or class II molecule. Insight into the precise composition and biology of self and non-self immunopeptidomes is essential to harness T cell mediated immunity to prevent, treat, or cure infectious diseases and cancers. T cell antigen discovery is an arduous task! The pioneering work in the early 1990s has made large-scale T cell antigen discovery possible. Thus, advancements in mass spectrometry coupled with proteomics and genomics technologies make possible T cell antigen discovery with ease, accuracy, and sensitivity. Yet we have only begun to understand the breadth and the depth of self and non-self immunopeptidomes because the molecular biology of the cell continues to surprise us with new secrets directly related to the source, and the processing and presentation of MHC ligands. Focused on MHC class I molecules, this review, therefore, provides a brief historic account of T cell antigen discovery and, against a backdrop of key advances in molecular cell biologic processes, elaborates on how proteogenomics approaches have revolutionized the field.

show abstract

Identification of GP100-derived, melanoma-specific cytotoxic T-lymphocyte epitopes restricted by HLA-A3 supertype molecules by primaryin vitro immunization with peptide-pulsed dendritic cells

Cited by 43 publications

References 31 publications

Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens

Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens

Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens

Know thy immune self and non‐self: Proteomics informs on the expanse of self and non‐self, and how and where they arise

Contact Info

Product

Resources

About