Selection of Ligands for Polyclonal Antibodies from Random Peptide Libraries: Potential Identification of (Auto)Antigens That May Trigger B and T Cell Responses in Autoimmune Diseases

Pathogenesis of juvenile chronic arthritis: genetic and environmental factors

“…The advent of more comprehensive approaches allowing genome-wide studies to be performed, the use of peptide libraries to look for relevant antigens36 and the further development of transgenic and gene knockout animal models is likely to herald greater understanding of the complex genetic traits and environmental triggers underlying the different forms of JCA. This, in turn, will enhance the prospect of developing more specific, effective and potentially curative treatments for these diseases.…”

The nature of target-unrelated peptides recovered in the screening of phage-displayed random peptide libraries with antibodies

“…They represent a significant handicap in applications in which serum or purified total IgGs are used as targets (e.g., if IgGs from donors having a particular disease are used to identify ligands that act as serologic markers for that disease). In these cases, reduction of TUP can be achieved by preadsorption of the input phage with IgGs from healthy donors, as was done by Sioud et al [74]. Selection of phage by xenoreactive antibodies present in human sera may be prevented by the use of carbohydrates having the Gal(a1,3)Gal epitope (e.g., melibiose, Galili et al [49]) in the phage-target incubation step.…”

“…Some of this high incidence may be explained by the fact that proline is overrepresented in many primary PDPLs ( [74], and references therein) . The widely used pIII-display PhD-C7C, PhD-7, and PhD-12 libraries from New England Biolabs (http://www.neb.com/neb/frame_tech.html and) and 2 of our 12 pVIII-based libraries also share this feature [29,75,76].…”

B-cell epitope prediction for peptide-based vaccine design

“…One mechanism already alluded to herein is positive selection of B cells whose surface immunoglobulins bind immunodominant B-cell epitopes, whereby activation of other B cells is suppressed (e.g., through preemptive binding of immunodominant B-cell epitopes by antibodies that renders other B-cell epitopes sterically inaccessible). Another mechanism is tolerance, i.e., difficulty of eliciting antibodies to certain B-cell epitopes even in the absence of immunodominant competitors, due to negative selection against either B cells themselves or T cells that might otherwise provide T-cell help to the B cells; this normally suppresses production of antibodies to self molecules and food components, thereby preventing deleterious hypersensitivity reactions [20,66,30,32,7]. These mechanisms are subject to imprinting, that is, the influence of past immune responses on future ones; as an immune response selects certain lymphocyte clones at the expense of others, it biases subsequent immune responses towards certain B-cell epitopes and away from others.…”

“…The plasticity of host immune systems has evolved to defend against pathogens, yet it is exploited by pathogens through deceptive imprinting that suppresses antibody responses to B-cell epitopes whose binding by antibodies interferes with infection [33,49,48]; pathogens thus present highly immunodominant Bcell epitopes as decoys [51,53,27] and even mimic normally tolerated B-cell epitopes (e.g., of host biomolecules) [37], although attempts at such mimicry may break normal tolerance to induce deleterious hypersensitivity reactions (e.g., antibodymediated autoimmune destruction of host biomolecules) [16,66]. In principle, deceptive imprinting and its sequelae can be overcome with vaccines that refocus antibody responses towards critical B-cell epitopes to suppress, disrupt or otherwise circumvent pathophysiological mechanisms (e.g., of infection and autoimmunity) [53,43,71]; but to actually design such vaccines demands comprehensive knowledge of disease-specific pathophysiology, which for infectious processes is complicated by host-pathogen coevolution [12].…”