Publisher Summary Turns are a fundamental class of polypeptide structure and are defined as sites where the peptide chain reverses its overall direction. In the past 20 years, the peptide field has witnessed major development, stimulated by the discovery of a host of bioactive peptides. Turn structures have been proposed and implicated in the bioactivity of several of these naturally occurring peptides. In addition, many structural details of turns have been derived from conformational studies of model peptides. During this same period, more than 100 complete protein structures have been elucidated in single-crystal X-ray studies. These examples document the rich diversity of structural patterns in the chain folds of native proteins. Turns are intrinsically polar structures with backbone groups that pack together closely and side chains that project outward. Such an array of atoms may constitute a site for molecular recognition, and indeed, the literature abounds with suggestions that turns serve as loci for receptor binding, antibody recognition, and post-translational modification. In peptides, turns are the conformations of choice for simultaneously optimizing both backbone–chain compactness (intramolecular nonbonded contacts) and side-chain clustering (to facilitate intermolecular recognition). Presence of turns in bioactive conformations may in fact also reflect the lack of alternative conformational possibilities. The aim of this chapter is to examine structural and functional roles of turns in peptides and proteins.

Turns in peptides and proteins.

The purpose of this article is to review the nature of the immune response to influenza virus both in hosts which experience natural infection, particularly man, and in hosts which are experimentally infected, particularly mice, Until recently, an article on this topic may well have contained only a rather superficial account of the properties of the virion with hardly a mention of the replication process. However, the past few years have seen great advances in two almost separate developments. On the one hand, detailed information is now available on the viral genome and the expression of viral proteins: there are complete amino acid sequences and X-ray crystallographic analysis of the two surface glycoproteins, the hemagglutinin and the neuraminidase; we have a greater understanding of the roles of gene reassortment and mutation in the generation of antigenic shift and drift, and of the mechanism of viral replication and assembly. On the other hand, and although there are still very significant gaps, there has been a great increase in our knowledge of the different classes of lymphocytes, particularly T cells, and to a lesser extent of other cell types involved in the immune response to this virus. Significant correlations in the case of human studies and the findings from cell transfer studies in experimental systems have made possible the allocation of particular roles to different cell types.

The immune response to influenza infection.

Studies in this laboratory have resulted in the delineation and synthetic verification of several complete protein antigenic structures that are recognized by antibodies More recently, for the first time, the full profiles of the sites that are recognized by T cell have been localized and confirmed by synthesis for two proteins, myoglobin and lysozyme These have thus far constituted the only complete antigenic strutures to be determined The availability of these antigenic structures has enabled us to investigate in detail the molecular and cellular parameters responsible for immune recognition, responses to, and control and regulation of these responses to protein antigens at the molecular and submolecular levels Moreover, these investigations have afforded general strategies for the synthetic mimicking of not only antigenic sites, but also protein binding sites involved in other biological activities

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1984.tb08516.x

Antigenic structures of proteins. Their determination has revealed important aspects of immune recognition and generated strategies for synthetic mimicking of protein binding sites.

A large-scale vaccination experiment involving a total of 138 cattle was carried out to evaluate the potential of synthetic peptides as vaccines against foot-and-mouth disease Four types of peptides representing sequences of foot-and-mouth disease virus (FMDV) C3 Argentina 85 were tested: A, which includes the G-H loop of capsid protein VP1 (site A); AT, in which a T-cell epitope has been added to site A; AC, composed of site A and the carboxy-terminal region of VP1 (site C); and ACT, in which the three previous capsid motifs are colinearly represented Induction of neutralizing antibodies, lymphoproliferation in response to viral antigens, and protection against challenge with homologous infectious virus were examined None of the tested peptides, at several doses and vaccination schedules, afforded protection above 40% Protection showed limited correlation with serum neutralization activity and lymphoproliferation in response to whole virus In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mutant FMDVs with amino acid substitutions at antigenic site A were identified This finding suggests the rapid generation and selection of FMDV antigenic variants in vivo In contrast with previous studies, this large-scale vaccination experiment with an important FMDV host reveals considerable difficulties for vaccines based on synthetic peptides to achieve the required levels of efficacy Possible modifications of the vaccine formulations to increase protective activity are discussed

A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants.

Antigen-antibody interaction. Synthetic peptides define linear antigenic determinants recognized by monoclonal antibodies directed to the cytoplasmic carboxyl terminus of rhodopsin.

This paper reports the antigenicity of the fusion region of the influenza virus hemagglutinin (HA). Two peptides, comprising the fusion region (residues 1-11 of the HA2 part of HA) of strain A and strain B influenza virus, were synthesized and their abilities to bind rabbit, goat, and human anti-influenza antibodies were determined. In addition, 30 anti-HA monoclonal antibodies were examined for their ability to bind the synthetic peptides. In quantitative immunoadsorbent titrations, the two peptides bound considerable amounts of antibodies in rabbit and goat antisera against virus or HA of the A or B strain as well as in several human sera from patients recovering from influenza A. Of the 30 anti-HA monoclonal antibodies, 5 bound completely and 4 bound partially to the peptides. Antibodies were raised in rabbits against the peptides by immunizing with peptide-bovine serum albumin conjugates or with the free peptides. Anti-peptide antibodies were bound by HA and by the intact virus of the respective strain. However, these antisera failed to exhibit significant virus neutralizing activity. In contrast, the monoclonal antibodies that reacted with these peptides inhibited viral infectivity. The results clearly show that residues 1-11 of HA2 represent an important antigenic site on influenza virus.

R G Webster

Papers

Localization, synthesis, and activity of an antigenic site on influenza virus hemagglutinin