Computational peptide dissection of Melan-a/MART-1 oncoprotein antigenicity.
ABSTRACT We have mapped the linear antigenic determinant of a commercial MAb raised in the mouse against the melanoma-associated-antigen Melan-A/MART-1. The B cell epitope on the Melan-A/MART-1 oncoprotein is located in the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP, within residues 102-106. The definition of the antigenic sequence on Melan-A/MART-1 oncoprotein was reached following analyses of MHC II binding potential and similarity level to the mouse proteome, that put into evidence the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP as the top scoring peptide in binding H2-A(d) molecules and the epitopic sequence residues 102-106 (i.e., the peptide sequence PAYEK) as having low-similarity level to the mouse proteome. Dot-blot epitope mapping immunoassay identified proline residue 102 as critical, based on its effect on antibody recognition. The present study adds to previous companion reports in validating the hypothesis that low-similarity to the host's proteome and binding potential to MHC II molecules are essential concurring factors in the modulation of the pool of epitopic sequences.
- SourceAvailable from: Jp Spinosa[Show abstract] [Hide abstract]
ABSTRACT: Sequence matching analyses show that Clostridium tetani neurotoxin shares numerous pentapeptides (68, including multiple occurrences) with 42 human proteins that, when altered, have been associated with epilepsy. Such a peptide sharing is higher than expected, nonstochastic, and involves tetanus toxin-derived epitopes that have been validated as immunopositive in the human host. Of note, an unexpected high level of peptide matching is found in mitogen-activated protein kinase 10 (MK10), a protein selectively expressed in hippocampal areas. On the whole, the data indicate a potential for cross-reactivity between the neurotoxin and specific epilepsy-associated proteins and may help evaluate the potential risk for epilepsy following immune responses induced by tetanus infection. Moreover, this study may contribute to clarifying the etiopathogenesis of the different types of epilepsy.Epilepsy research and treatment. 01/2014; 2014:236309.
- [Show abstract] [Hide abstract]
ABSTRACT: Epidemiologic data suggest that maternal microbial infections may cause fetal neurodevelopmental disorders, potentially increasing susceptibility to heavy psychopathologies such as schizophrenia, schizophreniform disorder, autism, pervasive developmental disorders, bipolar disorders, psychosis, epilepsy, language and speech disorders, and cognitive impairment in adult offspring. However, the molecular pathomechanisms underlying such a relationship are not clear. Here we analyze the potential role of the maternal immune response to viral infection in determining fetal brain injuries that increase the risk of neurological disorders in the adult. We use influenza infection as a disease model and human axon guidance pathway, a key process in the formation of neural network during midgestation, as a potential fetal target of immune insults. Specifically, we examined influenza A H1N1 hemagglutinin (HA), an antigenic viral protein, for amino acid sequence similarity to a random library of 188 axon guidance proteins. We obtain the results that (1) contrary to any theoretical expectations, 45 viral pentapeptide matches are distributed throughout a subset of 36 guidance molecules; (2) in 24 guidance proteins, the peptide sharing with HA antigen involves already experimentally validated influenza HA epitopes; and (3) most of the axon guidance vs HA peptide overlap is conserved among influenza A viral strains and subsets. Taken together, our data indicate that immune cross-reactivity between influenza HA and axon guidance molecules is possible and may well represent a pathologic mechanism capable of determining neurodevelopmental disruption in the fetus.Schizophrenia Bulletin 01/2013; · 8.61 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Aim: Notwithstanding a renewed interest in the application of immunotherapy as an alternative to chemotherapy and radiotherapy for the treatment of ovarian cancer (OC), and in spite of the available knowledge about ovarian tumor-associated-antigens, the search for a vaccine against OC remains a scientific and clinical challenge. Likewise, immunodiagnostics can detect only a late stage of the disease. Thus, the development of new therapeutic and diagnostic options is highly desirable. Methods: Based on the low-similarity hypothesis, which supports the concept that immunogenicity is preferentially associated to sequences with no/low-similarity to the host proteome, and using Protein Information Resource peptide match program, we searched the ovarian tumor antigen CA125 for amino acid sequences unique to CA125 and absent in the remaining human proteins. Results & conclusion: We identified a set of 159 pentapeptides unique to CA125 that might be used to design specific and effective immunological tools for diagnosis and treatment of OC.Immunotherapy 01/2014; 6(1):35-41. · 2.39 Impact Factor