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 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.

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.

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

1971 ◽  
Vol 133 (2) ◽  
pp. 216-230 ◽  
Author(s):  
G. M. Shearer ◽  
Edna Mozes ◽  
Michael Sela
Keyword(s):  
Genetic Control ◽  
Inbred Mouse ◽  
Phenotypic Expression ◽  
Mouse Strains ◽  
Spleen Cells ◽  
Chi Square ◽  
Synthetic Polypeptides ◽  
Chi Square Test ◽  
Synthetic Polypeptide ◽  
Syngeneic Recipient

DBA/1 mice are high responders to the (Phe, G) determinant of the synthetic polypeptide (Phe, G)-Pro--L, whereas SJL mice respond well to the Pro--L region of this macromolecule (6). In order to determine whether the phenomenon described above is related to the number of antigen-sensitive units detected for both specificities, and whether responses to these determinants can be transferred independently, graded and limiting inocula of spleen cells from SJL, DBA/1, and F1 donors were injected into X-irradiated, syngeneic, recipient mice with (Phe, G)-Pro--L. By this approach, one antigen-sensitive unit specific for (Phe, G) was detected in 1.7 x 106 and 8.5 x 106 spleen cells from immunized and nonimmunized DBA/1 donors, respectively. In contrast, one (Phe, G) relevant precursor was detected in 20 x 106 SJL spleen cells, irrespective of whether the donors had been immunized. On the other hand, for the Pro--L specificity, one limiting splenic precursor was found in 1.3 x 106 and in 3.4 x 106 cells for immunized and nonimmunized SJL donors, respectively; whereas one response unit was estimated for this determinant in 9.4 x 106 and in 38 x 106 spleen cells from immunized and nonimmunized DBA/1 mice. The findings reported here indicate that the phenotypic expression of the genetic control(s) for immune responsiveness to different immunopotent regions of (Phe, G)-Pro--L is directly correlated with the number of immunocompetent response units detected in two inbred mouse strains. In the spleens of immunized F1 donors, similar frequencies of one limiting precursor in 3.0 x 106 and in 2.8 x 106 cells were detected for (Phe, G) and Pro--L, respectively. The results of a chi-square test for independence of (Phe, G) and Pro--L responses in F1 animals is compatible with the hypothesis that the transferred spleen cells limiting the response to (Phe, G)-Pro--L are restricted to generate antibodies specific for only one of the two determinants of this macromolecule.

scholarly journals GENETIC CONTROL OF THE ANTIBODY RESPONSE IN INBRED MICE

1968 ◽  
Vol 128 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Hugh O. McDevitt ◽  
Marvin L. Tyan
Keyword(s):  
Genetic Control ◽  
Antibody Formation ◽  
Inbred Mice ◽  
Progeny Testing ◽  
Secondary Immune Response ◽  
Linkage Studies ◽  
Spleen Cells ◽  
The Third ◽  
Backcross Populations ◽  
Synthetic Polypeptide

The transfer of spleen cells from (C3H x C57Bl/6) F1 mice, capable of responding to (T,G)-A--L, into irradiated C3H parental recipients, normally incapable of responding to (T,G)-A--L, transfers the ability to make either a primary or secondary immune response to this synthetic polypeptide antigen. This localizes the genetic control of the ability to respond to the spleen cell population and indicates that the genetic control is exerted upon a process directly related to antibody formation. Studies with congenic strains of mice and linkage studies in segregating backcross populations show that the ability to respond to (T,G)-A--L and (H,G)-A--L is linked to the H-2 locus and can thus be localized to the IXth mouse linkage group. Note Added in Proof: Of the three possible recombinant animals noted in Tables IV and V, two were infertile. The third animal was not a recombinant, since progeny testing and reimmunization showed that this animal was an H-22/H-2k heterozygote capable of responding well to (T,G)-A--L.

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