The genetic control of the immune response to different antigenic determinants within the synthetic polypeptide poly (His,Glu)-polyPro–poly Lys

1974 ◽  
Vol 4 (7) ◽  
pp. 463-467 ◽  
Author(s):  
Edna Mozes ◽  
S. Shaltiel ◽  
M. Sela
Keyword(s):  
Immune Response ◽  
Genetic Control ◽  
Antigenic Determinants ◽  
Synthetic Polypeptide

scholarly journals GENETIC CONTROL OF THE ANTIBODY RESPONSE

1967 ◽  
Vol 126 (5) ◽  
pp. 969-978 ◽  
Author(s):  
Hugh O. McDevitt ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Glutamic Acid ◽  
Genetic Control ◽  
Antigenic Determinants ◽  
Polyglutamic Acid ◽  
Cross Reactions ◽  
Cba Mice ◽  
Related Series ◽  
Synthetic Polypeptide

CBA and C57 mice were tested for their ability to make an immune response to a related series of branched, multichain synthetic polypeptide antigens in which the antigenic determinants on the amino termini of the branched side chains were systematically varied. Neither strain responded to the polyglutamic acid determinant. Both strains responded well and equally to the poly(phenylalanine, glutamic acid) determinants. CBA mice responded poorly, and C57 mice responded well to two different antigens bearing poly(tyrosine, glutamic acid) determinants. CBA mice responded well, and CS7 mice responded poorly to two different antigens bearing poly(histidine, glutamic acid) determinants. The genetic control of the immune response to (H,G)-A--L appears to be dominant and polygenic, as it has been shown to be for (T,G)-A--L. The related antigens used in this study show extensive cross-reactions with antisera against other members of the related series.

scholarly journals ANTIBODY RESPONSE OF INBRED MOUSE STRAINS TO ORDERED TETRAPEPTIDES OF TYROSINE AND GLUTAMIC ACID ATTACHED TO MULTICHAIN POLYALANINE OR POLYPROLINE

1974 ◽  
Vol 140 (2) ◽  
pp. 349-355 ◽  
Author(s):  
Edna Mozes ◽  
Michal Schwartz ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Glutamic Acid ◽  
Inbred Mouse ◽  
Cross Reactivity ◽  
Antigenic Determinants ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Linked Gene ◽  
Random Peptide ◽  
Synthetic Polypeptide

Five inbred mouse strains which represent high and low responders to the random synthetic polypeptide poly(LTyr,LGlu)-polyDLAla--polyLLys, designated (T, G)-A--L, to which the immune response is controlled by an H-2-linked gene, were immunized with three ordered tetrapeptides composed of tyrosine and glutamic acid attached either to multichain poly-DL-alanine or to polyproline. Only one of the three antigenic determinants, namely tyrosyl-tyrosyl-glytamyl-glutamic acid (T-T-G-G), resembled the random peptide (T, G) in the pattern of immune responses elicited against it, and in the cross-reactivity of the specific antibodies with (T, G)-A--L. The immune response pattern to the other two ordered tetrapeptides, T-G-T-G and G-T-T-G, was different from that obtained with (T, G)-A--L, and no cross-reactivity was detected between the antibodies provoked with these peptides and (T, G)-A--L. Thus, it is suggested that T-T-G-G is a major determinant in the random (T, G)-A--L.

scholarly journals CELLULAR BASIS OF THE GENETIC CONTROL OF IMMUNE RESPONSES TO SYNTHETIC POLYPEPTIDES

1970 ◽  
Vol 132 (4) ◽  
pp. 613-622 ◽  
Author(s):  
Edna Mozes ◽  
G. M. Shearer ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Genetic Control ◽  
Relative Number ◽  
Precursor Cells ◽  
Spleen Cells ◽  
Low Responders ◽  
Synthetic Polypeptides ◽  
Low Responder ◽  
Synthetic Polypeptide ◽  
High Responders

SJL mice are high responders to the synthetic multichain polypeptide antigen (T,G)-Pro--L, whereas DBA/1 mice are low responders (10, 11). In order to determine whether the genetic control of immune response can be correlated with the number of antigen-sensitive precursor cells, spleen cell suspensions from normal and immunized SJL and DBA/1 donor mice were transplanted into lethally X-irradiated syngeneic recipients (incapable of immune response) along with (T, G)-Pro--L. Anti-(T, G)-Pro--L responses (donor-derived) were assayed in the sera of the hosts 12–16 days later. By transplanting graded and limiting numbers of spleen cells, inocula were found which contained one or a few antigen-sensitive precursors reactive with the immunogen. Using this method to estimate the relative numbers of such cells for the high responder SJL strain, one precursor was detected in ∼1.3 x 106 and ∼7.2 x 106 spleen cells from immunized and normal donors, respectively. In contrast, one precursor was detected in about 30 x 106 spleen cells from low responder DBA/1 mice, irrespective of whether the donors had been immunized. These results indicate that the genetic control of immunity to the synthetic polypeptide antigen investigated is directly correlated to the relative number of precursor cells reactive with the immunogen in high and low responder strains.

Genetic control of the immune response to a thymus independent synthetic polypeptide

1974 ◽  
Vol 1 (1) ◽  
pp. 357-369 ◽  
Author(s):  
Anne -Marie Schmitt-Verhulst ◽  
Edna Mozes ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Genetic Control ◽  
Synthetic Polypeptide

scholarly journals GENETIC CONTROL OF THE IMMUNE RESPONSE

1972 ◽  
Vol 135 (6) ◽  
pp. 1259-1278 ◽  
Author(s):  
Hugh O. McDevitt ◽  
Beverly D. Deak ◽  
Donald C. Shreffler ◽  
Jan Klein ◽  
Jack H. Stimpfling ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Control ◽  
Linkage Test ◽  
Progeny Testing ◽  
Crossover Event ◽  
Extensive Analysis ◽  
Synthetic Polypeptides ◽  
Synthetic Polypeptide

Eleven strains of mice bearing recombinant H-2 chromosomes derived from known crossover events between known H-2 types were immunized with a series of branched, multichain, synthetic polypeptide antigens [(T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L]. Results with nine of the eleven H-2 recombinants indicated that the gene(s) controlling immune response to these synthetic polypeptides (Ir-1) is on the centromeric or H-2K part of the recombinant H-2 chromosome. Results with two of the eleven recombinant H-2 chromosomes indicated that Ir-1 was on the telomeric or H-2D part of the recombinant H-2 chromosome. Both of these recombinants were derived from crossovers between the H-2K locus and the Ss-Slp locus near the center of the H-2 region. One of these recombinants, H-2y, was derived from a known single crossover event. These results indicate that Ir-1 lies near the center of the H-2 region between the H-2K locus and the Ss-Slp locus. The results of a four-point linkage test were consistent with these results. In 484 offspring of a cross designed to detect recombinants between H-2 and Ir-1, only two putative recombinants were detected. Both of these recombinants were confirmed by progeny testing. Extensive analysis of one of them has shown that the crossover event occurred within the H-2 region. (Testing of the second recombinant is currently under way.) Thus, in the linkage test, recombinants between H-2 and Ir-1 are in fact intra-H-2 crossovers. These results permit assignment of Ir-1 to a position between the H-2K locus and the Ss-Slp locus.

scholarly journals THE GENETIC CONTROL OF ANTIBODY SPECIFICITY

1969 ◽  
Vol 130 (6) ◽  
pp. 1263-1278 ◽  
Author(s):  
Edna Mozes ◽  
Hugh O. McDevitt ◽  
Jean-Claude Jaton ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Genetic Control ◽  
Binding Capacity ◽  
Major Gene ◽  
Antibody Specificity ◽  
Heavy Chains ◽  
The One ◽  
Genetically Determined ◽  
Cross Inhibition ◽  
Synthetic Polypeptide

The immune response to a synthetic polypeptide built on multichain polyproline, poly-L-(Tyr,Glu)-poly-L-Pro-poly-L-Lys [(T,G)-Pro--L], in the offspring of a cross between DBA/1 and SJL mice is under a genetic control superficially similar to the one operating for the immune response to a similar synthetic polypeptide built on multichain polyalanine, poly-L-(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys [(T,G)-A--L], in the offspring of a cross between CBA and C57 mice. In both cases, the genetic control is a quantitative trait in which the major gene(s) is (are) dominant and the trait is not linked to any of the known structural genes coding for mouse immunoglobulin heavy chains. However, the genetic control of response to (T, G)-Pro--L, designated immune response-3 (Ir-3), is qualitatively different from the one operating for (T,G)-A--L [immune response-1 (Ir-1)] in that it is not linked to the histocompatibility-2 (H-2) locus. A study of the immune response to a related polypeptide built on multichain polyproline, poly-L-(Phe,Glu)-poly-L-Pro-poly-L--Lys [(Phe, G)-Pro--L], in the DBA/1 x SJL cross has shown a genetic control of antibody specificity. F1 x DBA/1 backcross anti-(Phe, G)-Pro--L sera segregate in their ability to bind (T,G)-Pro--L, and there is no linkage of anti-(T,G)-Pro--L binding capacity with the H-2s allele of the SJL grandparent. F1 x SJL anti-(Phe, G)-Pro-L sera segregate in their capacity to bind poly-L-(Phe,Glu)-poly-D,L-Ala-poly-L-Lys [(Phe, G)-A--L] and the ability to bind (Phe, G)-A--L is clearly linked to the H-2q allele from the DBA/1 grandparent. Thus, in mice all responding well to a given antigen [(Phe, G)-Pro--L], the specificity of the antibodies produced [i.e., anti-(Phe,G) or anti-prolyl] is genetically determined. Cross-inhibition of binding m (DBA/1 x SJL)F1 anti-(Phe,G)-Pro--L antisera indicates that the anti-(Phe,G) and anti-prolyl specificities are a function of two separate and largely non-crossreacting antibody populations.

scholarly journals Genetic control of the immune response to staphylococcal nuclease. VII. Role of non-H-2-linked genes in the control of the anti-nuclease antibody response

1978 ◽  
Vol 147 (2) ◽  
pp. 396-408 ◽  
Author(s):  
DS Pisetsky ◽  
JA Berzofsky ◽  
DH Sachs
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Genetic Control ◽  
Heavy Chain ◽  
Staphylococcal Nuclease ◽  
Antigenic Determinants ◽  
Structural Genes ◽  
Antibody Titers ◽  
Freund's Adjuvant

The role of non-H-2-linked genes in the control of the antibody response to staphylococcal nuclease has been investigated. 3 wk after immunization with nuclease in complete Freund's adjuvant, strain A/J (H-2 a) mice produced significantly higher titers of antibody than strain B10.A (H-2(a)) mice, whereas mice of strains A.BY (H-2(b)) and B10 (H-2(b)) produced barely detectable titers. With hyperimmunization, A/J and A.BY mice reached the same peak levels for antibody titers, both severalfold higher than those reached by B10.A and B10 mice. Analysis of the specificity of antibodies by assessment of binding to two fragments of nuclease showed similarities between strains of the same H-2 haplotype. These results suggest that although H-2-1inked genes determined initial responsiveness at 3 wk and the relative proportions of antibodies directed toward different antigenic determinants on the nuclease molecule, non-H-2-linked genes determined the overall magnitude of the hyperimmuneresponse. Measurement of the affinity of the antibodies to the nuclease fragment (1-126) showed that strains B10 and B10.A produced antibodies with 7- to 10-fold higher affinity than comparable antibodies from strains A.BY and A/J. In a backcross of (B10.A × A/J) × B10.A, the level of antibody segregated independently of the Ig-1(e) C(H) allotype and the A/J anti-nuclease idiotypes. Thus, a gene(s) linked to neither H-2 nor heavy chain structural genes appears to control the aggregate response to antigenic determinants on the nuclease molecule independent of subspecificities of these antibodies or their idiotype.

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