scholarly journals The antibody response to myoglobin is independent of the immunized species. Analysis in terms of replacements in the antigenic sites and in environmental residues of the cross-reactions of fifteen myoglobins with sperm-whale myoglobin antisera raised in different species

1980 ◽  
Vol 191 (3) ◽  
pp. 681-697 ◽  
Author(s):  
S S Twining ◽  
H Lehmann ◽  
M Z Atassi
Keyword(s):  
Amino Acid ◽  
Antibody Response ◽  
Three Dimensional ◽  
Sperm Whale ◽  
Cross Reactivity ◽  
Antigenic Structure ◽  
Amino Acid Substitutions ◽  
Antigenic Sites ◽  
The Cross ◽  
Sperm Whale Myoglobin

The recent determination of the entire antigenic structure of sperm-whale myoglobin with rabbit and goat antisera has permitted the examination of whether the antigenic structure recognized by antibodies depends on the species in which the antisera are raised. Also, by knowledge of the antigenic structure, the molecular factors that determine and influence antigenicity can be better understood in terms of the effects of amino acid substitutions occurring in the antigenic sites and in the environmental residues of the sites. In the present work, the myoglobins from finback whale, killer whale, horse, chimpanzee, sheep, goat, bovine, echidna, viscacha, rabbit, dog, cape fox, mouse and chicken were examined for their ability to cross-react with antisera to sperm-whale myoglobin. By immunoadsorbent titration studies with radioiodinated antibodies, each of these myoglobins was able to bind antibodies to sperm-whale myoglobin raised in goat, rabbit, chicken, cat, pig and outbred mouse. It was found that the extent of cross-reaction of a given myoglobin was not dependent on the species in which the antisera were raised. This indicated that the antibody response to sperm-whale myoglobin (i.e. its antigenic structure) is independent of the species in which the antisera are raised and is not directed to regions of sequence differences between the injected myoglobin and the myoglobin of the immunized host. Indeed, in each antiserum from a given species examined, that antiserum reacted with the myoglobin of that species. The extent of this auto-reactivity for a given myoglobin was comparable with the general extent of cross-reactivity shown by that myoglobin with antisera raised in other species. The cross-reactivities and auto-reactivities (both of which are of similar extents for a given myoglobin) can be reasonably rationalized in terms of the effects of amino acid substitutions within the antigenic sites and within the residues close to these sites. These findings confirm that the antigenicity of the sites is inherent in their three-dimensional locations.

scholarly journals Distance calculation of residues neighbouring to lysozyme antigenic sites. Site-neighbouring residues whose evolutionary substitution can modify the characteristics and binding energy of the sites

1980 ◽  
Vol 187 (1) ◽  
pp. 163-172 ◽  
Author(s):  
M Z Atassi ◽  
A L Kazim
Keyword(s):  
Amino Acid ◽  
Binding Sites ◽  
Binding Capacity ◽  
Antigenic Structure ◽  
Amino Acid Substitutions ◽  
Protein Binding Sites ◽  
X Ray ◽  
Distance Calculation ◽  
Antigenic Sites ◽  
Nearest Neighbours

By using the antigenic structure of lysozyme determined in this laboratory and the X-ray co-ordinates we have calculated the closest-atom distances between each of the residues in the three antigenic sites and all the other amino acids of the lysozyme molecule. These calculations enabled us to identify the nearest neighbours to each of the site residues. Thus the immediate environment of each site residue is described. For the three antigenic sites there is a total of 71 neighbouring residues. The effects of evolutionary amino acid substitutions in site-neighbouring residues on the binding capacity of protein binding sites in general and on protein antigenic sites in particular are discussed. These, together with the direct replacements in site residues, will acount for the major effects. However, the limitations of this treatment are stressed. The smaller effects on antigenic sites of replacements at once-removed and even at more distant locations, which, when they become cumulative, could be considerable, are brought to attention, together with any influences of conformational readjustments that can take place as a result of evolutionary amino acid replacements.

scholarly journals Computer Simulations of the Humoral Immune System Reveal How Imprinting Can Affect Responses to Influenza HA Stalk with Implications for the Design of Universal Vaccines

2018 ◽  
Author(s):  
Christopher S. Anderson ◽  
Mark Y. Sangster ◽  
Hongmei Yang ◽  
Sidhartha Chaudhury ◽  
David J. Topham
Keyword(s):  
Immune System ◽  
B Cells ◽  
Antibody Response ◽  
Cross Reactivity ◽  
Memory B Cells ◽  
Gillespie Algorithm ◽  
Humoral Immune ◽  
Antigenic Sites ◽  
Humoral Immune System ◽  
The Cross

AbstractBackgroundSuccessful vaccination against the H1N1 Influenza A virus has required the continuous development of new vaccines that are antigenically similar to currently circulating strains. Vaccine strategies that can increase the cross-reactivity of the antibody response, especially to conserved regions, are essential to creating long-lasting immunity to H1N1 viruses. How pre-existing immunity affects vaccine-induced antibody cross-reactivity is still not well understood.MethodsAn immunological shape space of antigenic sites of hemagglutinin (HA) was constructed using viral sequence data. A Gillespie Algorithm-based model of the humoral immune system was used to simulate B cell responses to A/California/07/2009 (CA09) HA antigen after prior immunization with an antigenically similar or dissimilar strain. The effect of pre-existing memory B cells and antibody on the resulting antibody responses was interrogated.ResultsWe found increased levels of highly-cross-reactive antibodies after immunization with antigenically dissimilar strains. This increase was dependent on pre-existing memory B cells. Furthermore, pre-existing antibody also interfered with the cross-reactive antibody response, but this effect occurred irrespective of the priming antigen.ConclusionThese findings suggest that vaccination by divergent strains will boost highly-cross-reactive antibodies by selectively targeting memory B cells specific to conserved antigenic sites and by reducing the negative interference caused by pre-existing antibody.

scholarly journals Nearest-neighbour analysis of myoglobin antigenic sites. Nearest-neighbour residues whose replacement can alter the environment of binding-site residue(s) and thus change their characteristics and binding capability

1980 ◽  
Vol 191 (3) ◽  
pp. 673-680 ◽  
Author(s):  
A L Kazim ◽  
M Z Atassi
Keyword(s):  
Binding Capacity ◽  
Antigenic Site ◽  
Sperm Whale ◽  
Antigenic Structure ◽  
Nearest Neighbour ◽  
X Ray ◽  
Antigenic Sites ◽  
Binding Capability ◽  
Sperm Whale Myoglobin ◽  
Neighbour Analysis

By using the known antigenic structure of sperm-whale myoglobin previously determined in this laboratory and the X-ray co-ordinates for the myoglobin molecule, we have calculated the nearest-atom distances between each of the residues of the antigenic sites and all the other amino acids of the myoglobin molecule. These calculations have enabled us to identify the nearest-neighbour residues to each of the residues in the five antigenic sites, and which thus describe the immediate molecular environment of the sites. The influences of chemical changes or replacements in these environmental residues on the binding capacity of an antigenic site, when considered together with replacements directly in the antigenic sites, are expected to account for the major effects and will be extremely useful in explaining the cross-reactions of myoglobins from various species. However, it is stressed that the analysis has limitations due to the qualitative estimates of the effects, the influences of substitutions of once-removed or even at more distant locations (especially when they are cumulative) and finally the influences of any conformational re-adjustments when these occur as a result of the replacement(s).

scholarly journals Prediction and conformation by synthesis of two antigenic sites in human haemoglobin by extrapolation from the known antigenic structure of sperm-whale myoglobin

1977 ◽  
Vol 167 (1) ◽  
pp. 275-278 ◽  
Author(s):  
A L Kazim ◽  
M Z Atassi
Keyword(s):  
Sperm Whale ◽  
Antigenic Structure ◽  
Homologous Proteins ◽  
Human Haemoglobin ◽  
Antigenic Sites ◽  
Inductive Effects ◽  
Structural Analogy ◽  
Starting Model ◽  
Sperm Whale Myoglobin

The complete antigenic structure of sperm-whale myoglobin was previously determined in our laboratory. By structural analogy with myoglobin, two regions in human haemoglobin were predicted to comprise antigenic sites. One region was on the alpha-chain [alpha-(15-23)] and the other on the beta-chain [beta-(16-23)]. These two regions were synthesized, purified and characterized, and their immunochemistry was studied. Each peptide was able specifically to bind considerable amounts of haemoglobin antibodies. In a set of homologous proteins, barring any drastic conformational or electrostatic inductive effects exerted by the substitutions, and allowing for obstruction due to subunit interaction, the determination of the antigenic structure of one protein may serve as a useful starting model for the others.

The amino acid sequence of human myoglobin and its minor fractions

1974 ◽  
Vol 186 (1084) ◽  
pp. 249-279 ◽  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Three Dimensional ◽  
Sperm Whale ◽  
Dimensional Structure ◽  
Human Haemoglobin ◽  
Human Myoglobin ◽  
Main Component ◽  
Haemoglobin Molecule ◽  
Sperm Whale Myoglobin

The complete amino acid sequence of human skeletal myoglobin is described. That of heart myoglobin is found by homology to be the same. When myoglobin is prepared some minor fractions may be obtained besides the main component. They are shown to be artefacts arising from deamidations. The likely three-dimensional structure of human myoglobin is discussed, taking that of sperm-whale myoglobin as a reference. Human myoglobin is compared with the α - and β -chains of human haemoglobin. There is a noteworthy similarity of internal residues and haem contacts, but little resemblance of sites where the haemoglobin chains form dimeric and tetrameric contacts, when they become subunits of the haemoglobin molecule.

The crystal structure of myoglobin. VI. Seal myoglobin

1960 ◽  
Vol 258 (1293) ◽  
pp. 181-201 ◽  
Keyword(s):  
Tertiary Structure ◽  
Heavy Atom ◽  
Three Dimensional ◽  
Sperm Whale ◽  
Fourier Synthesis ◽  
Heavy Atoms ◽  
Isomorphous Replacement ◽  
Unit Cells ◽  
The Common ◽  
Sperm Whale Myoglobin

Myoglobin from the common seal ( Phoca vitulina ) when crystallized from ammonium sulphate forms monoclinic crystals with space group the unit cell, a = 57·9Å, b = 29·6Å, c = 106·4Å, β = 102°15', contains four molecules. The method of isomorphous replacement has been used in an investigation of the centrosymmetric b -axis projection in which it has been possible to determine signs for nearly all the h0l reflexions having spacings greater than 4Å. Three independent heavy-atom derivatives were employed and the signs so determined have been used to compute a map of the electron density projected on the (010) plane. This projection has been interpreted in terms of the molecule of sperm-whale myoglobin, as deduced by Bodo, Dintzis, Kendrew & Wyckoff (1959) from a three-dimensional Fourier synthesis to 6Å resolution. The results of the interpretation show that the two myoglobin molecules are very similar in form (tertiary structure) in spite of the differences in their amino-acid composition. The relative orientation of the two unit cells with respect to the myoglobin molecule is given and a comparison is made of the positions of the heavy atoms in each molecule.

The Amino-Acid Sequence of Sperm Whale Myoglobin: Chemical Studies

Nature ◽  
1961 ◽  
Vol 190 (4777) ◽  
pp. 663-665 ◽  
Author(s):  
A. B. EDMUNDSON ◽  
C. H. W. HIRS
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Sperm Whale ◽  
Chemical Studies ◽  
Sperm Whale Myoglobin
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