Clustering of rare peptide segments in the HCV immunome

Abstract

Our previous research and a comprehensive meta-analysis of data from the literature on epitope mapping has revealed that the B cell epitope repertoire is allocated to rare peptide motifs, i.e., antigenic peptide sequences endowed with a low level of similarity to the host proteome. From a clinical point of view, low-similarity peptides able to evoke an immune response appear to be of special interest for the rational design of vaccines for poorly treatable diseases such as hepatitis-C virus (HCV) infection. Indeed, low similarity peptides would guarantee the highest specificity and lowest cross-reactivity, i.e., effectiveness without adverse side-effects. In this study, aimed at gaining further information for the development of effective anti-HCV peptide-based vaccines, the HCV epitopes recognized by human antibodies and currently catalogued in the Immune Epitope Data Base (IEDB) were examined for pentamer sequence similarities to the human proteome. We report that the analyzed HCV determinants are characterized by the presence of fragment absent from (or scarcely represented in) human proteins. These data confirm the low-similarity hypothesis, according to which a low-similarity to the host proteome defines the nonself character of microbial antigens and modulates peptide immunogenicity. Moreover, this study indicates a concrete and safe immunotherapeutic approach which might be used in a universal anti-HCV vaccine.

A quantitative description of the peptide sharing between poliovirus andHomo sapiens

“…(8)(9)(10)(11)(12)(20)(21)(22)(23)(24)(25)(26)(27)(28)(46)(47)(48) The extent of peptide sharing between polio and human proteomes is high, and rises to striking numerical values at the pentapeptide level, with 18,239 matches extensively sparsed among 9410 human proteins (supplemental Table S1). Given the current evaluation of the human proteome as containing 25,635 proteins (see at http://www.ebi.ac.uk/integr8), 36.7% of the human proteome contain at least one viral pentapeptide.…”

“…Endogenous retroviruses represent about 8% of the human genome (3) ; numerous cell-homologous genes are present in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8 (4) ; human IL-10 has a matching counterpart in Epstein-Barr virus gene, BCRF1 (viral IL-10) (5)(6)(7) ; a widespread and ample peptide overlapping connects hepatitis C virus (HCV) and Homo sapiens proteomes and only a limited number of peptide motifs are unique to the virus at the pentapeptide level. (8)(9)(10)(11) Aligning the HCV nucleotide sequence to the human genome also reveals a relevant viral-versus-human commonality. Basically, analysis of the unique HCV pentapeptide set at the nucleotide level shows that the maximum genetic difference between HCV and humans is, at most, represented by trinucleotides.…”

Peptide Sharing between Bordetella Pertussis Proteome and Human Sudden Death Proteins: A Hypothesis for a Causal Link

“…At the same time, the present data, together with other reports from this lab [74][75][76][77][78], offer new perspectives for developing safe (immuno)therapeutic tools [79,80]. Indeed, peptide-based vaccines and therapeutic approaches that selectively exclude crucial peptide sharing will possess the required antimicrobial efficacy without the harmful potential to trigger self autoantigens.…”

Developing an anti-Campylobacter jejunivaccine

“…(10)(11)(12) The methodology is based on the hypothesis that only rare peptide modules have an immune potential, whereas common repeated peptide motifs are immunologically silent. (13)(14)(15)(16)(17) Recently, this hypothesis has been evaluated in the context of infectious diseases by defining the similarity level between the human proteome and immunopeptidomes from microbial organisms such as hepatitis C virus (HCV), (5,(17)(18)(19)(20) influenza H5N1, (21) human immunodeficiency virus (HIV), (22,23) and Mycobacterium tuberculosis. (24) Here, we apply this scientific rationale to Campylobacter jejuni, and search for peptide targets that might be used to develop anti-C. jejuni immunotherapy.…”

“…(3,4) Within the field of immunology, this approach makes it possible to single out specific peptide sequences from disease-associated proteins, enabling the collection and handling of immunopeptidome libraries for use in diagnosis and immunotherapy. (5) In this framework, we utilize perfect peptide match analysis in order to identify peptide sequences that are able to elicit therapeutic antibodies in cancer (6)(7)(8)(9) or neutralize pathogenic circulating auto-antibodies in autoimmune diseases. (10)(11)(12) The methodology is based on the hypothesis that only rare peptide modules have an immune potential, whereas common repeated peptide motifs are immunologically silent.…”