Epitopes evaluation

Jarvis, L.M. and Pritchard, D.I. (1992) An evaluation of the role of carbohydrate epitopes in immunity to Trichinella spiralis. Parasite Immunology 14, 489-501. 

To study the role of lysine residues in susceptibility to formalin fixation, the amino acid composition of immunoreactive peptides (to various monoclonal antibodies) was studied. Each peptide was evaluated to determine if immu-noreactivity was lost after formalin fixation. Formalin sensitivity was correlated with the peptides amino acid composition. The first step in the method is biopanning from a peptide combinatorial library with a monoclonal antibody. The peptides that bind to the antibody were tested for their sensitivity to formalin fixation. Some peptides remain immunoreactive whereas others do not. The peptides were then sequenced to look for differences between those that were sensitive to formaldehyde versus those that were not. The goal was to find whether there is a particular amino acid that is present in formalin-sensitive epitopes but absent in formalin-resistant epitopes, or vice versa. An advantage of this approach is that it is open-ended, without excluding any amino acids. 

To evaluate the influence of structural parameters governed by the cyclophosphazene core concerning the valency and the spatial orientation of epitopes, as well as the nature of linkers directly related to the ligation technique used for the mannoside incorporation, the authors performed preliminary kinetic turbidimetric assays with Con A. Insoluble cross-linked complexes formed rapidly for all compounds, without marked difference for the hexavalent analogues. On the other hand, the incorporation of additional mannosyl units led merely to statistical binding-affinity enhancements, notably for the less-dense decamer 194, which presents favorable extended intersugar distances. 

In the second research strategy, plant viruses have been utilized as pliable genetic platforms for protein expression. Three formats have been developed, and the one that has undergone the most extensive evaluation is the display of epitopes on the surface of the virus as fusions with the viral coat protein. This epitope-display system... 

Adjuvants enhancing HLA class I-restricted CTL responses are especially needed for treatment or prevention of chronic viral diseases and infections linked to intracellular pathogens, and for cancer immunotherapy. Among the very few adjuvants licensed for human use, we evaluated the capacity of IRIV to enhance HLA class I-restricted CTL responses in vitro. We addressed IRIV-elicited immune responses and the induction of CTL specific to IM58 66 and Melan-A/Mart-127-35 epitopes. Proliferation assays, cytokine expression studies, and phenotypes of CD4+ T-cells demonstrated that IRIV... 

CTL induction experiments consistently demonstrate that IRIV indeed enhance induction of HLA class I-restricted CTL specific for IMsg-ee and Melan-A/Mart-127-35 epitopes. CTL induction in presence of irradiated or nonirradiated CD4+ cells showed that IRIV CTL adjuvance requires CD4+ T-cell activation. Remarkably, IRIV CTL adjuvance observed in our in vitro studies is solely due to IRIV immunogenicity and independent of peptide delivery and protection capacities, as peptides were not encapsulated in nor attached to IRIV. Further studies are warranted to clarify whether and to what extent delivery, protection, and immunogenic capacities of IRIV synergize in CTL adjuvance. The fact that IRIV adjuvance was observed in relation to the tumor-associated epitope Melan-A/Mart-127-35 encourages further evaluation of IRIV as potential adjuvants in cancer... 

These MHG class I alterations have been evaluated by the analysis of the panel of tumor samples with immunohistochemistry or flow cytometry in disrupted tumor cell suspensions as well as established tumor cell lines using a series of mAbs directed against HLA class I monomorphic, HLA-A or -B locus-specific, HLA-allelic epitopes or against various APM components including TAPI, TAP2, tpn and the different LMP subunits. The results demonstrated that rates of HLA class I and APM component losses in tumor cell lines strongly varied between the different tumor types analyzed. 

At the epitope level, the Immune Epitope Database and Analysis Resource (IEDB) is the largest immune epitope database so far (http //www.immuneepitope.org/). IEDB has stored more than 65,000 antibody and T-cell epitopes since the database was established in 2004 (9). These immune epitopes cover various species (e.g., humans, nonhuman primates, and rodents) that have been well studied in the areas of infectious diseases (9). Because all stored epitopes in IEDB are manually curated from experimental studies, the data in IEDB have often been used as the gold standard for evaluating in silico epitope prediction tools (10). 

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