Journal: medRxiv

Article Title: HPV T-cell epitope landscape: systematic mapping of distribution, conservation, and HLA promiscuity towards rational vaccine design

doi: 10.1101/2025.11.03.25339381

Figure Lengend Snippet: Proteome analysis of 485 HPV T-cell epitopes with defined peptide length and protein annotations, showing: (a) number of experimentally validated CD8⁺ (Class I) and CD4⁺ (Class II) T-cell epitopes identified per HPV protein; and (b) correlation between protein length and epitope count for HPV and SARS-CoV-2 proteins, with linear regression (solid) and 95% confidence interval (shaded). Immunogenicity analysis of 316 HPV T-cell epitopes with defined response rates, illustrating: (c) distribution of epitopes with available response rate data, showing proportional representation of HPV proteins; and (d) immunogenicity profiles (response rate) across amino acid positions of individual HPV proteins, highlighting distinct regions of epitope clustering.

Article Snippet: Functionally validated HPV T-cell epitopes were curated from the Immune Epitope Database (IEDB), filtered by length, HLA restriction, and immunogenicity.

Techniques: Immunopeptidomics

Journal: medRxiv

Article Title: HPV T-cell epitope landscape: systematic mapping of distribution, conservation, and HLA promiscuity towards rational vaccine design

doi: 10.1101/2025.11.03.25339381

Figure Lengend Snippet: Proteome analysis of 485 HPV T-cell epitopes with defined peptide length and protein annotations (a-d) , showing: (a) genomic map of HPV proteins by reading frame (HPV-16; Ref.Seq: NC_001526.4), colored by functional class (oncoprotein E5, E6, E7=vermillion, replication E1, E2, E4=navy-hatched, structural L1, L2=green-dotted) with amino acid lengths indicated and dashed lines connecting spliced segments; (b) number of studies reporting epitopes per protein; (c) number of epitopes per protein based on T-cell subsets; and (d) epitope density showing the number of epitopes studied every 100 amino acids of each protein. Genotype analysis of 484 HPV T-cell epitopes with defined genotype annotations (e-h) , illustrating: (e) the number of epitopes per HPV type stratified by T-cell subset (CD8⁺ =yellow-hatched, CD4⁺=light blue-dotted), IARC-defined high-risk types are highlighted in bold orange; (f) proportion of epitopes restricted to high-risk versus low-risk groups, with p-value and odds ratio (OR, 95% CI) shown (reference=low-risk); (g) distribution of epitopes across HPV proteins (E1–L2) stratified by risk group (high-risk=vermilion-hatched, low-risk=gray-dotted) with global p-value indicated; and (h) proportion of epitopes restricted to a single HPV type (gray) versus those conserved across multiple types (cross-type epitopes, pink).

Article Snippet: Functionally validated HPV T-cell epitopes were curated from the Immune Epitope Database (IEDB), filtered by length, HLA restriction, and immunogenicity.

Techniques: Functional Assay

Journal: medRxiv

Article Title: HPV T-cell epitope landscape: systematic mapping of distribution, conservation, and HLA promiscuity towards rational vaccine design

doi: 10.1101/2025.11.03.25339381

Figure Lengend Snippet: Immunogenicity analysis of 316 HPV T-cell epitopes with defined response rates (a-b), showing: (a) proportion of subjects tested with CD4 + (light blue-dotted) and CD8 + (yellow-hatched) epitopes showing positive (colored) versus negative (gray) immune responses, with p value and OR [95% CI] indicated; (b) proportion of subjects tested with epitope form oncoprotein E5-E7 (vermillion), replication E1-E4 (navy blue-hatched) and structural L1-L2 (green-dotted) protein epitopes showing positive (colored) versus negative (gray) immune responses, with global p value and OR [95% CI] indicated. Analysis of 289 epitopes with defined HLA-annotation and 219 allele-level-restricted (c-f) , illustrating: (c) number of CD4⁺ (light blue-dotted) and CD8⁺ (yellow-hatched) epitopes across all HLA-annotated (total) and allele-level restricted datasets, with total n indicated below each group; (d) proportion of class I (yellow-hatched) and Class II (light blue-dotted) epitopes classified as mono-allelic or multi-allelic (HLA-promiscuous) binders, with OR [95% CI] and p value indicated; (e) number of class I (CD8⁺, yellow-hatched) and class II (CD4⁺, light blue-dotted) restricted epitopes mapped to individual HLA alleles; (f) correlation between response rate and HLA promiscuity among CD8⁺ and CD4⁺ epitopes. Each dot represents a unique epitope, colored by HPV protein and scaled by the number of subjects tested (dot size, quartiles shown in legend).

Article Snippet: Functionally validated HPV T-cell epitopes were curated from the Immune Epitope Database (IEDB), filtered by length, HLA restriction, and immunogenicity.

Techniques: Immunopeptidomics

Journal: medRxiv

Article Title: HPV T-cell epitope landscape: systematic mapping of distribution, conservation, and HLA promiscuity towards rational vaccine design

doi: 10.1101/2025.11.03.25339381

Figure Lengend Snippet: Analysis of 219 HLA allele-restricted illustrating: (a) comparison of the number of epitopes per HLA allele between Class I (CD8⁺) and Class II (CD4⁺) restrictions; and (b–c) correlations between the number of unique HLA alleles and total epitopes per protein for CD8⁺ (b, orange) and CD4⁺ (c, light blue) T-cell epitopes, with Spearman’s ρ and p-values indicated.

Article Snippet: Functionally validated HPV T-cell epitopes were curated from the Immune Epitope Database (IEDB), filtered by length, HLA restriction, and immunogenicity.

Techniques: Comparison

Journal: medRxiv

Article Title: HPV T-cell epitope landscape: systematic mapping of distribution, conservation, and HLA promiscuity towards rational vaccine design

doi: 10.1101/2025.11.03.25339381

Figure Lengend Snippet: Conservation analysis of 485 unique T-cell epitopes towards 454 reference genomes, showing: (a) distribution of CD8⁺ (yellow) and CD4⁺ (light blue) epitopes by peptide length and number of HPV types covered; (b) cross-type coverage of unique epitopes across HPV proteins; (c) number of unique T-cell epitopes identified across HPV genotypes, grouped by high-risk (orange) and low-risk (gray) types; (d) proportion and number of HPV types covered by each epitope, compared between high-risk (orange) and low-risk (gray) groups; and (e) epitope distribution across the HPV proteome, showing the localization of CD8⁺ (yellow) and CD4⁺ (light blue) T-cell epitopes in high-risk and low-risk types, grouped by functional protein classes (oncoprotein, replication, and structural).

Article Snippet: Functionally validated HPV T-cell epitopes were curated from the Immune Epitope Database (IEDB), filtered by length, HLA restriction, and immunogenicity.

Techniques: Functional Assay

Journal: medRxiv

Article Title: HPV T-cell epitope landscape: systematic mapping of distribution, conservation, and HLA promiscuity towards rational vaccine design

doi: 10.1101/2025.11.03.25339381

Figure Lengend Snippet: Analysis of 485 unique T-cell epitopes mapped to 454 reference genomes showing (a) comparison of HPV types coverage between CD4⁺ and CD8⁺ T-cell epitopes, where each dot represents a unique epitope, and horizontal lines show medians with interquartile ranges. Analysis of 316 epitopes across 20 HLA-restricted alleles for both MHC Class I (CD8⁺) and Class II (CD4⁺) T cells, showing (b) response rate (% positive donors) comparison between binders and non-binders.

Article Snippet: Functionally validated HPV T-cell epitopes were curated from the Immune Epitope Database (IEDB), filtered by length, HLA restriction, and immunogenicity.

Techniques: Comparison

Journal: medRxiv

Article Title: HPV T-cell epitope landscape: systematic mapping of distribution, conservation, and HLA promiscuity towards rational vaccine design

doi: 10.1101/2025.11.03.25339381

Figure Lengend Snippet: HLA prediction analysis of 485 T-cell epitopes across 20 HLA allele supertypes for both CD4⁺ and CD8⁺ T cells, illustrating: (a) distribution of epitopes classified as non-binders versus predicted binders, stratified by T-cell type (CD8⁺ vs CD4⁺); (b) frequency distribution of the number of HLA alleles bound per epitope; (c–d) distribution of predicted binder epitopes across HPV proteins for CD8⁺ and CD4⁺, shown by mono-allelic (grey) versus multi-allelic epitopes (colored); (e–f) predicted binding capacity of HPV epitopes across HLA Class I (CD8⁺) and Class II (CD4) alleles, showing the number of weak (light-dotted) and strong (dark) binders for each allele; and (g– h) heatmaps showing the distribution of predicted binding strength across HPV proteins and HLA alleles for Class I (CD8⁺, yellow) and Class II (CD4⁺, light blue), with strong binders (colored) and weak binders (gray) mapped across structural (green), oncoprotein (orange), and replication-associated (light blue) antigens.

Article Snippet: Functionally validated HPV T-cell epitopes were curated from the Immune Epitope Database (IEDB), filtered by length, HLA restriction, and immunogenicity.

Techniques: Binding Assay