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

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.

1967 ◽  
Vol 126 (5) ◽  
pp. 969-978 ◽  
Author(s):  
Hugh O. McDevitt ◽  
Michael Sela

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.


1977 ◽  
Vol 145 (1) ◽  
pp. 123-135 ◽  
Author(s):  
J A Berzofsky ◽  
A N Schechter ◽  
G M Shearer ◽  
D H Sachs

The relative proportions of antibodies of different specificities within antisera raised to native staphylococcal nuclease have been studied in several strains of mice in which the antibody response has been shown to be under H-2-linked Ir-gene control. A method was developed in which binding to different radiolabeled fragments of nuclease was titrated against increasing fragment concentration until the binding capacity of the antiserum for that fragment was saturated. In comparing the low responder (H-2b) strain C57BL/10 with its congenic high responder counterpart B10.A (H-2a), it was found that the two strains made markedly and reproducibly different proportions of antibodies to different determinants on native nuclease. Since these two strains differ only at H-2, and therefore have identical immunoglobulin structural gene repertoires, we conclude that H-2-linked Ir genes can control the response to different determinants on the same antigen molecule independently of one another. This result suggests a possible role of H-2-linked genes in the selection of specific B cells.


1977 ◽  
Vol 146 (6) ◽  
pp. 1603-1612 ◽  
Author(s):  
D S Pisetsky ◽  
D H Sachs

Rat antisera detecting binding site-specific idiotypic determinants on anti-nuclease antibodies from A/J mice have been used to define the A/J anti-nuclease idiotype and to investigate its genetic linkage as a variable region marker. Analysis of the segregation of the A/J idiotype in progeny of the backcross (B10.A X A/J) X B10.A showed linkage of the idiotype to the Ig-1e heavy chain allotype locus. There was, however, a very high apparent frequency of recombination, with 7 of 101 backcross animals having a recombinant phenotype. All of these putative recombinants were accounted for by Ig-1b/Ig-1b homozygotes which bore the A/J idiotype, and none by Ig-1b/Ig-1e heterozygotes lacking the idiotype. On progeny testing of these animals in another backcross to B10.A the recombinant trait bred true. If this idiotype is indeed a marker for variable region structural genes, then the germ line gene pool must be very large or there must be special genetic mechanism to account for the increased recombinational frequency observed.


Author(s):  
Jay A. Berzofsky ◽  
David S. Pisetsky ◽  
Ronald H. Schwartz ◽  
Alan N. Schechter ◽  
David H. Sachs

1971 ◽  
Vol 133 (5) ◽  
pp. 987-1003 ◽  
Author(s):  
Carolyn S. Pincus ◽  
Michael E. Lamm ◽  
Victor Nussenzweig

The ability of passively administered antibody to suppress the immune response against homologous antigenic determinants while concomitantly enhancing the response against other unrelated determinants of the same antigen molecule has been established in two distinct antigen-antibody systems: (a) guinea pig γ2-immunoglobulin + passive anti-F(ab')2 antibody, where suppression of anti-F(ab')2 antibody synthesis is accompanied by enhancement of the anti-Fc response; and (b) human secretory IgA + passive anti-serum IgA antibody, where suppression of antibody production against the α and L chains accompanies augmentation of the response to the secretory component. The mechanisms of the suppressive and enhancing effects are probably unrelated for the following reasons: (a) Enhancement of the response to certain determinants may be obtained without discernible suppression of the response to the homologous determinants; and (b) the F(ab')2 fragments of passive antibody can mediate immune suppression but were not observed to enhance the response against the unrelated determinants of the same antigen molecule. Also, the timing for achieving maximum suppression or enhancement of antibody formation is not the same; enhancement was obtained only at a later time. Both the enhancement and suppressive effects were obtained with the purified γG fraction of antisera. This finding rules out an exclusive role of γM antibody in the enhancement phenomenon.


Author(s):  
Ourania S. Kotsiou ◽  
Dimitrios Papagiannis ◽  
Evangelos C. Fradelos ◽  
Dimitra I. Siachpazidou ◽  
Garifallia Perlepe ◽  
...  

Background: In this work we aimed to evaluate antibody-response longevity to SARS-CoV-2 infection and/or vaccination in one of the Greek communities that was worst hit by the pandemic, Deskati, five months after a previous serosurveillance and nine months after the pandemic wave initiation (October 2020). Methods: The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. Results: A total of 69 subjects, who previously tested positive or negative for COVID-19 antibodies, participated in the study. We found that 48% of participants turned positive due to vaccination and 27% of participants were both previously infected and vaccinated. All previously infected participants retained antibodies to the virus, irrespective of their vaccination status. The antibody titers were significantly higher in previously infected participants that had been vaccinated than those who were unvaccinated and in those that had been previously hospitalized for COVID-19 than those with mild disease. Conclusions: Antibody responses to SARS-CoV-2 infection were maintained nine months after the pandemic. Vaccination alone had generated an immune response in almost half of the population. Higher antibody titers were found in the case of vaccination in previously infected subjects and especially in those with severe disease leading to hospitalization


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