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M Z Atassi

Publications and source records attributed to M Z Atassi.

At least 199 records · Page 11Linked to original sources
PubMed1979

Genetic control of immune response to sperm whale myoglobin in mice. II. T lymphocyte proliferative response to the synthetic antigenic sites.

The genetic control of T lymphocyte proliferative response to the five synthetic antigenic sites of myoglobin, two synthetic nonantigenic control peptides, and one "nonsense" peptide was determined in independent and recombinant strains of mice. In all the strains examined, the nonantigenic control peptides and the "nonsense" peptide did not invoke a response in myoglobin-primed mice. Further, when mice were not primed with whole myoglobin, no response was obtained with any of the antigenic sites. Haplotypes H-2d, H-2f, and H-2s are higher responders to sites 1 and 2, whereas haplotypes H-2d and H-2s are high responders to site 5. Response to site 3 may be controlled by a non-H-2-linked gene. Site 4 can stimulate H-2b and H-2k haplotypes that are nonresponders to the whole myoglobin. Studies with the recombinant strains suggested that Ir genes to sites 1 and 2 map in the I-A subregion and I-C subregion and were designated Ir-Mb-1,2(A) and Ir-Mb-1,2(C). Ir genes to sites 4 and 5 mapped only in the I-A subregion and were designated Ir-Mb-4(A) and Ir-Mb-5(A). These studies suggest that individual antigenic sites in a molecule are controlled by unique Ir genes.

Animals↗
PubMed1978

Boundary refinement of the lysozyme antigenic site around the disulphide bond 6-127 (site 1) by 'surface-simulation' synthesis.

1. We have previously shown that an antigenic site (site 1) in native lysozyme resides around the disulphide bond 6-127 and, by classical synthesis of nine disulphide peptides, the antigenic site was accurately narrowed down to the structure Cys((6))-Arg((14))-[Cys((6))-Cys((127))] -Gly((126))-Arg((128)). Only a few residues on this disulphide peptide were proposed to be involved in the reactivity with antibody. However, this lacked direct verification and the role of Arg-128 remained uncertain. 2. In the present work, several peptides were designed and synthesized by the surface-simulation concept devised in our laboratory. These enabled the precise definition of the site as well as the investigation of its conformational and directional requirements. 3. The results showed that the antigenic site (site 1) is made up of the spatially contiguous surface residues: Arg-125, Arg-5, Glu-7, Arg-14, Lys-13. The surface-simulation synthetic peptide Arg-Gly-Gly-Arg-Gly-Glu-Gly-Gly-Arg-Lys (which does not exist in native lysozyme, but copies a surface region of it) accounted entirely for the maximum expected reactivity of the site (i.e. about one-third of the total antigenic reactivity of lysozyme). An immunoadsorbent of the peptide also removed about one-third of the total lysozyme antibodies. 4. The antigenic site exhibited restricted conformational freedom. The achievement of the full reactivity of the site by surface-simulation synthesis requires the appropriate choice of spacer separation between its reactive residues. The surface-simulation synthetic site exhibits the same mono-directional preference (Arg-125 to Lys-13) for the rabbit and goat antisera so far tested. The site describes a line which encircles a part (3.01 nm in C((alpha))-to-C((alpha)) distance from Arg-125 to Lys-13) of the surface of the molecule.

Amino Acid Sequence↗
PubMed1978

The precise and entire antigenic structure of native lysozyme.

The exact boundary, residue, conformational and directional definitions of the three antigenic sites of native hen's egg-white lysozyme are described. The results clearly reveal that the three antigenic sites account quantitatively for the total antigenic reactivity of the protein. Thus the entire antigenic structure of lysozyme has now been precisely determined and is briefly discussed here, together with the power of the surface-stimulation synthetic concept.

Amino Acid Sequence↗
PubMed1978

Differentiation of the contribution of the two subunits of lutropin to its in vivo activity.

Porcine and ovine lutropins were acetimidated at amino groups to various degrees and the effects of the modification on the induction of ovarian ornithine decarboxylase activity were examined. A drastic (84%) loss of biological activity was observed upon modification of two amino groups in porcine lutropin. The results with ovine lutropin derivatives were quite similar. Circular dichroism measurements showed no conformational changes and dissociation into subunits was not observed in the derivatives. Accordingly, the loss of biological activity was not a by-product of conformational changes. It was concluded that lutropin carries a single binding site which is constructed by surface residues or regions located on both the alpha- and beta-subunits of the hormone.

Animals↗
PubMed1978

First consequences of the determination of the entire antigenic structure of sperm-whale myoglobin.

By using the antigenic structure of sperm-whale Mb as a model we have established that the antigenicity of its sites is independent of any sequence identities between the injected myoglobin and the Mb of the immunized animal. Furthermore, the ability to produce in rabbits autoantibodies to rabbit Mb and the successful extrapolation of the antigenic structure of sperm-whale Mb to human hemoglobin strongly demonstrated that the antigenicity of certain parts of a protein molecule is primarily dependent on the uniqueness of their conformational locations.

Amino Acid Sequence↗
PubMed1978

The precise and entire antigenic structure of lysozyme: implications of surface-simulation synthesis and the molecular features of protein antigenic sites.

Intensive research in the author's laboratory over a 10-year period has now culminated in the precise determination of the entire antigenic structure of native hen egg-white lysozyme. The protein carries three antigenic sites. Each site is made up of spatially adjacent surface residues that are not in direct peptide linkage. The residues of each site describe an imaginary line which circumscribes part of the surface topography of the protein and act functionally towards the antibody as if they are in direct peptide bond linkage. The reactivity of each site is fully satisfied by an appropriate surface-simulation synthetic peptide, and the three synthetic sites account for the full immunochemical reactivity of the native protein. Each site is subject to conformational restrictions and exhibits directionality which is a function of side chain orientations. The antigenic sites of myoglobin and lysozyme are compared. It is proposed that antigenic sites of the type found in myoglobin are called "continuous sites", while antigenic sites of the type seen in lysozyme are defined as "discontinuous sites".

Amino Acid Sequence↗
PubMed1978

Genetic control of immune response to sperm whale myoglobin in mice. I. T lymphocyte proliferative response under H-2-linked Ir gene control.

Studies on the genetic control of immune response to sperm whale myoglobin were initiated. As demonstrated in this paper, the T lymphocyte proliferative response to whale myoglobin is under H-2-linked Ir gene control. Mice of H-2d, H-2f, and H-2s haplotypes were high responders to the myoglobin, whereas haplotypes H-2b, H-2k, H-2p, H-2q, and H-2r were low responders. The Ir gene(s) was localized between H-2K and H2D regions, since the recombinant strain A.TL (KsIkSkDd) was a low responder and A.TH (KsIsSsDd) was a high responder. Further studies with recombinant strains revealed that the expression of the high-responder I-Ad or Ias alleles was sufficient to give a good response, since strains D2.GD (d d b b b b b b) and B10.HTT (s s s s k k k d) were high responders. The expression of the I-Cd allele in strains B10.A (k k k k k d d d) and B10.A(5R) (b b b k k d d d) also gave high response, and thus suggested a second Ir gene, derived from the H-2d haplotype. The finding that expression of the I-Cs allele in B10.S(8R) (k k ? ? s s s s) did not result in high response suggests the lack of the second Ir gene in the high-responder H-2s haplotype.

Animals↗
PubMed1977

Can an antibody-combining site be mimicked synthetically? The possible surface simulation synthesis of two antibody-combining sites complementary to two antigenic sites of lysozyme.

Our recent determination of the complete antigenic structure of native lysozyme was made possible by our introduction of the "surface simulation" synthetic concept. The remarkable success afforded by this strategy in the synthetic construction of antigenic sites prompted us to investigate whether it can be applied to mimic antibody-combining sites. Two peptides, designed to be complementary to antigenic sites 2 and 3 of lysozyme, were synthesized and their immunochemistry was studied. Each of the two complementary peptides exhibited an appreciable inhibitory activity towards the reaction of lysozyme with its antisera. Peptide immunoadsorbents bound only lysozyme and not antibody or myoglobin. Neither of the two peptides had any immunochemical activity in the myoglobin or bovine serum albumin immune systems. Furthermore, it was shown that three control synthetic peptides of myoglobin, of similar charge but different sequence, had no inhibitory effect on the lysozyme immune reaction. The evidence indicates that the antibody-combining sites sgainst antigenic sites 2 and 3 of native lysozyme were successfully mimicked synthetically, at least in terms of binding function.

Antigens↗
PubMed1977

Enzymic and immunochemical properties of lysozyme. Accurate definition of the antigenic site around the disulphide bridge 30-115 (site 3) by 'surface-simulation' synthesis.

1. Previous reports from this laboratory have shown that both Lys-33 and Lys-116 are parts of an antigenic site in native lysozyme. Similar studies of tyrosine derivatives indicated that one or both of Tyr-20 and Tyr-23 are located in or very close to an antigenic site in lysozyme. The site, which was located around the disulphide bridge 30-115, was recently shown unequivocally to include the residues Tyr-20, Arg-21, Lys-116, Asn-113, Arg-114, Phe-34 and Lys-33. This was confirmed by the ;surface-simulation' synthetic approach that we have recently developed, in which the foregoing eight surface residues were directly linked via peptide bonds, with intervening spacers where appropriate, into a single peptide. The peptide does not exist in native lysozyme, but simulates a surface region of it. 2. In the present work several surface-simulation peptides were synthesized representing various parts of the region, to determine the minimum structural feature that retains full antigenic reactivity and to investigate if the spatially constructed antigenic site has a preferred direction. 3. The peptide Lys-Asn-Arg-Gly-Phe-Lys exhibited a remarkable inhibitory activity towards the immune reaction of lysozyme and accounted entirely for the maximum expected reactivity of the site in the native protein (i.e. about one-third of the total lysozyme reactivity). An immunoadsorbent of the peptide bound about one-third of the total antibody to lysozyme. 4. The residues Tyr-20 and Arg-21 are not part of the site. The previously reported immunochemical effect observed on nitration of Tyr-20 was due to a deleterious ionic effect exerted by the modified tyrosine residue on the adjacent Lys-96, which is in an entirely different antigenic site of lysozyme. Thus the modification of Tyr-20 impairs the reactivity of an adjacent antigenic site, even though the residue itself is not part of a site. The conformational and immunochemical implications of this finding are discussed. 5. The antigenic site therefore comprises the five spatially adjacent residues Lys-116, Asn-113, Arg-114, Phe-34, Lys-33. The antigenic site exhibited a preferred direction (Lys-116 to Lys-33), since the reverse surface-simulation synthetic sequence was immunochemically inefficient. The site describes a line which circumscribes part [2.1nm in C((alpha))-C((alpha)) distance from Lys-116 to Lys-33] of the surface of the molecule.

Antibodies↗
PubMed1977

Prediction and conformation by synthesis of two antigenic sites in human haemoglobin by extrapolation from the known antigenic structure of 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.

Amino Acid Sequence↗