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M Z Atassi

Publications and source records attributed to M Z Atassi.

At least 181 records · Page 10Linked to original sources
PubMed1980

Antibodies to synthetic antibody-combining sites. Antibodies against a surface-simulation peptide with antibody-combining activity toward lysozyme antigenic site 3 react with lysozyme antibodies.

Recently, we reported the synthesis and immunochemistry of two peptides designed, by complementarity and surface-simulation synthesis, to mimic antibody-combining sites against two antigenic sites of lysozyme. In the present work antibodies were raised against one of these peptides, which is complementary to antigenic site 3 of lysozyme, to determine whether these antibodies will react with anti-lysozyme antibodies. Radioiodinated antipeptide antibodies were bound by immunoadsorbents of the immune IgG from two goats anti-lysozyme antisera but not by adsorbents of myoglobin, non-immune goat IgG or immune IgG of antisera against cytochrome c. The binding of anti-peptide antibodies to adsorbents of anti-lysozyme antibodies was fully inhibited by free lysozyme but not by bovine serum albumin, human hemoglobin A, horse cytochrome c or bovine ribonuclease A. Thus, antisera against an antibody-combining site can be raised by immunizing with a peptide which probably does not exist in the antibody but is designed by surface-simulation synthesis to mimic an antibody-combining site.

Animals↗
PubMed1980

Antibody combining sites can be mimicked synthetically. Surface-simulation synthesis of the phosphorylcholine-combining site of myeloma protein M-603.

By applying the concept of 'surface-simulation' synthesis to the combining site of the myeloma protein M-603 we were able to mimic synthetically its phosphorylcholine-binding characteristics. The synthetic surface-simulation peptide was found to bind to phosphorylcholine, whereas a control peptide that had the same amino acid composition but a different sequence showed little or no binding activity. The specificity of the binding was further confirmed by inhibition studies in which the surface-simulation peptide, but not the control peptide, inhibited the binding of 125I-labelled surface-simulation peptide to phosphorylcholine. Furthermore, the surface-simulation peptide was found to completely inhibit the binding of the native myeloma protein, M-603, to phosphorylcholine. The control peptide was unable to inhibit this binding. These findings suggest that surface-simulation synthesis can be effectively employed to mimic synthetically antibody combining sites, and may in the future be a valuable tool with which to manipulate the immune response to clinically important antigens.

Animals↗
PubMed1980

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.

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.

Amino Acid Sequence↗
PubMed1980

Haemoglobin binding with haptoglobin. Unequivocal demonstration that the beta-chains of human haemoglobin bind to haptoglobin.

Haptoglobin binding to haemoglobin and its isolated alpha- and beta-chains was studied by use of a highly sensitive solid-phase radiometric assay. As expected, adsorbents of haemoglobin bound 125I-labelled haptoglobin more efficiently than did adsorbents of the alpha-chain. However, unexpectedly, adsorbents of the beta-chain were found to be essentially identical with those of the alpha-chain in their ability to bind haptoglobin. These results demonstrate, unequivocally, the ability of beta-chains to bind to haptoglobin, and indicate that this assay is particularly convenient and useful for studying haptoglobin interactions with haemoglobin and its alpha- and beta-chains.

Haptoglobins↗
PubMed1979

Localization and verification by synthesis of five antigenic sites of bovine serum albumin.

Recently we have shown that the major antigenic sites of bovine serum albumin exhibit functional equivalence progessively increasing with the time at which antibodies are obtained after the first immunization. Analysis of our recent immunochemical findings and the known covalent structure of bovine serum albumin have enabled us to predict the locations of five antigenic sites of bovine serum albumin. The predicted locations were synthesized, and immunochemical studies with late-course antisera showed them to constitute antigenic sites of native bovine serum albumin.

Animals↗
PubMed1979

Immunochemistry of serum albumin. VI. A dynamic approach to the immunochemical cross reactions of proteins using serum albumins from various species as models.

Antisera against bovine serum albumin were raised in two rabbits. Serial bleedings were obtained at different times after the first immunization, and antisera from these serial bleedings were not mixed but were kept and studied separately. The immunochemical cross-reactions of these antisera with serum albumins from bovine, goat, sheep, porcine, horse, human and chicken were determined by immunoadsorbent studies. These were done by titration so that the values of maximum (plateau) binding by each albumin of radioiodinated antibodies were determined. In each rabbit, the immunochemical cross-reactivity was not static but increased progressievly with time after the first immunization. In the interval 7 days to 398 days the increases in cross-reaction were extremely large. pH dissociation studies revealed that, together with the increase in cross-reactivity of a given albumin with time after immunization, there was a restriction in the antibody heterogeneity towards populations possessing higher affinity. These results provide a rational explanation for the different values of cross-reactivities for a given albumin from different laboratories. The findings are analyzed in relation to the antigenic structure of albumin and their significance in evolutionary studies discussed.

Animals↗
PubMed1979

Use of immunoadsorbents for the study of antibody binding to sperm whale myoglobin and its synthetic antigenic sites.

Conditions for preparing immunoadsorbents of sperm-whale myoglobin and its five synthetic antigenic sites and for desorption of radiolabeled antibodies from the immunoadsorbents were studied. In immunoadsorbent titration studies, the sum of the amounts of antibodies bound in the plateau (maximum binding) by the adsorbents of the five sites accounted quantitatively for the entire (100%) antibody response to sperm-whale myoglobin.

Animals↗
PubMed1979

Structure and activity of ragweed antigen E. II. Allergenic crossreactivity of the subunits.

Recently we have reported the isolation of the two subunits (alpha and beta) of ragweed antigen E (AgE) in their active form. In the present work we have compared the allergenic activity of the two subunits with native AgE by the radioallergosorbent test (RAST) and by inhibition of the RAST. Also, the amounts of IgE antibodies in 30 ragweed-sensitive sera bound to alpha and beta subunits as well as native AgE were measured by RAST. In all individuals the percentage of RAST binding was greatest to native AgE; however, varying patterns of reactivity to alpha and beta subunits were noted. In RAST inhibition experiments, free beta subunit was equally effective in inhibiting the binding of IgE antibody (from a pooled ragweed-sensitive sera) to immoblized alpha or beta subunit. Similarly, fluid-phase alpha subunit inhibited in a comparable manner the binding of IgE antibody to solid-phase alpha or beta subunits. In further RAST inhibition experiments 7 x 10(-13) moles of fluid-phase native AgE was required for 50% inhibition of the binding of IgE antibody to solid-phase native AgE. Larger molar amounts of fluid phase beta (3.5 x 10(-11) and alpha (3 x 10(-10) were needed for 50% inhibition of the binding of IgE antibody to solid-phase native AgE. AgE allergenicity as measured by RAST could not be totally reconstituted by recombination of equimolar quantities of alpha and beta subunits. Less than 1 x 10(-12) moles of fluid-phase native AgE inhibited the binding of IgE antibody to solid-phase alpha or beta, greater than 50%. Finally, the isolated chains are bioligcally active as demonstrated by their ability to provoke wheal-and-flare skin reactions in subjects allergic to ragweed pollen, and the activities of the chains were approximately equivalent on a weight basis to native AgE.

Allergens↗
PubMed1979

Genetic control of the immune response to hen's egg-white lysozyme in mice. I. Antibody and T-lymphocyte proliferative responses to the native protein.

We have initiated studies to determine whether the antibody and T-lymphocyte proliferative responses to lysozyme and its antigenic sites is genetically controlled in mice. Mice of the H-2f, H-2k and H-2p were high responders, while haplotypes H-2b, H-2d, H-2r and H-2s were low responders. Studies with recombinants indicated that the immune response is controlled by two H-2I region loci, one being in the I-A subregion and the other may be in the I-C subregions.

Animals↗