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 COMPARATIVE ANALYSIS OF ANTIGEN-BINDING T CELLS IN GENETIC HIGH AND LOW RESPONDER MICE

1974 ◽  
Vol 140 (5) ◽  
pp. 1180-1188 ◽  
Author(s):  
Günter J. Hämmerling ◽  
Hugh O. McDevitt
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Comparative Analysis ◽  
Antibody Response ◽  
Mouse Serum ◽  
Antigen Binding ◽  
Albumin Binding ◽  
Low Responders ◽  
Low Responder ◽  
High Responders

[125I](T,G)-A--L-binding T cells have been studied in mice whose ability to mount an immune response to (T,G)-A--L is under control of the H-2-linked Ir-1A gene. Nonimmunized high and low responder mice have approximately the same frequency of T-ABC. Following immunization, T-ABC proliferated only in high responders, but not in low responders, indicating expression of Ir-1A in T cells. When, for comparison, [125I]arsanyl-mouse serum albumin binding B and T cells were investigated in mice whose antibody response to the hapten arsanyl is controlled by an allotype-linked Ir gene, it was found that following immunization the number of B-ABC increased only in high responders. In contrast, T-ABC proliferated to the same extent in both high and low responders, suggesting exclusive expression of the allotype-linked Ir gene in the B-cell line. Preliminary studies indicate that anti-Ia sera inhibit neither B-ABC nor T-ABC.

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

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 An estimation of the frequency of precursor cells which generate cytotoxic lymphocytes.

1976 ◽  
Vol 143 (6) ◽  
pp. 1562-1567 ◽  
Author(s):  
M A Skinner ◽  
J Marbrook
Keyword(s):  
Immune Response ◽  
Culture System ◽  
Precursor Cells ◽  
Cytotoxic Lymphocytes ◽  
Spleen Cells ◽  
Cytotoxic Response ◽  
Cell Mediated Immune Response

The cell-mediated immune response has been generated in vitro with a polyacrylamide culture system which allows the segregation of foci (clones?) of cytotoxic lymphocytes. Using the method of limiting dilutions, the frequency of precursor cells in CBA spleen cells able to generate a cytotoxic response against DBA mastocytoma is estimated at 1 per 1,700 cells.

Sympathetic immunoregulation: difference between high- and low-responder animals

1982 ◽  
Vol 242 (1) ◽  
pp. R30-R33 ◽  
Author(s):  
A. del Rey ◽  
H. O. Besedovsky ◽  
E. Sorkin ◽  
M. Da Prada ◽  
G. P. Bondiolotti
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Quantitative Relationship ◽  
Spleen Weight ◽  
Low Responder ◽  
Sympathetic Nervous ◽  
High Responders

A quantitative relationship is reported between the magnitude of the immune response of rats to sheep red blood cells and diminution of splenic norepinephrine (NE). A decrease in concentration and content of NE in the spleen on day 3 after immunization was evident in both high- and low-responder animals, whereas a diminished concentration of NE persisted only in the high responders. This continuing NE diminution in high-responder animals is associated with increase in spleen weight, probably attributable to blood accumulation. These findings are consonant with the concept that the sympathetic nervous system is involved in immunoregulation.

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 CONTRIBUTION OF DIFFERENT CELL TYPES TO THE GENETIC CONTROL OF IMMUNE RESPONSES AS A FUNCTION OF THE CHEMICAL NATURE OF THE POLYMERIC SIDE CHAINS (POLY-L-PROLYL AND POLY-DL-ALANYL) OF SYNTHETIC IMMUNOGENS

1972 ◽  
Vol 135 (5) ◽  
pp. 1009-1027 ◽  
Author(s):  
G. M. Shearer ◽  
Edna Mozes ◽  
Michael Sela
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Genetic Control ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
High Responder ◽  
Side Chains ◽  
Low Responder ◽  
Synthetic Polypeptide ◽  
Marrow Cells

Genetic regulation of immunological responsiveness was studied at the cellular level by comparing the limiting dilutions of immunocompetent cells from spleen, thymus, and bone marrow of high and low responders as a function of the poly-L-prolyl and poly-DL-alanyl side chains of two synthetic polypeptide immunogens. The spleens of immunized and unimmunized high responder DBA/1 mice were found to contain respectively, 18- and 7-fold more limiting precursor cells specific for (Phe, G)-A--L than the spleens of SJL low responder donors. These results, using a synthetic polypeptide built on multichain poly-DL-alanine, confirm the findings reported for polypeptides built on multichain poly-L-proline (1, 2), that there is a direct correlation between immune response potential and the relative number of immunocompetent precursors stimulated. Cell cooperation between thymocytes and bone marrow cells was demonstrated for both (T, G)-Pro--L and (Phe, G)-A--L. Limiting dilutions of thymus and bone marrow cells in the presence of an excess amount of the complementary cell type indicated an eightfold lower number of detected (T, G)-Pro--L-specific precursors in DBA/1 (low responder) marrow when compared with SJL (high responder) marrow. No differences were observed in the frequency of relevant high and low responder thymocytes for the (T, G)-Pro--L immunogen. These results are similar to those reported for the (Phe, G)-Pro--L (3). In contrast to the cellular studies reported for the Pro--L series of immunogens, the marrow and thymus cell dilution experiments for (Phe, G)-A--L revealed genetically associated differences in both the marrow and thymus populations of immunocytes from high (DBA/1) and low (SJL) responders. In addition to a fivefold difference in limiting marrow cell precursors (similar to that seen in the Pro--L studies), a striking difference was observed between the helper cell activity of high responder DBA/1 and low responder SJL thymocytes. This difference was indicated by the observation that low responder thymocyte dilutions followed the predictions of the Poisson model, whereas dilutions of high responder thymocytes did not conform to Poisson statistics. Transfers of allogeneic thymus and marrow cell mixtures from DBA/1 and SJL donors confirmed the syngeneic dilution studies showing that the genetic defect of immune responsiveness to (Phe, G)-A--L is expressed at both the thymus and marrow immunocompetent cell level. The parameters presently known for genetic control of immune responses specific for (Phe, G) (Ir-1 gene) and for Pro--L (Ir-3 gene) have been compared. The Ir-1 and Ir-3 genes are not only distinct by genetic linkage tests (to H-2) (5, 6, 9), but they are also seen to be different by cellular studies. Furthermore, expression of low responsiveness within a given cell population was shown to depend on the chemical structure of the whole immunogenic macromolecule.

scholarly journals GENETIC CONTROL OF THE ANTIBODY RESPONSE TO POLY-L(TYR,GLU)-POLY-D,L-ALA--POLY-L-LYS IN C3H↔CWB TETRAPARENTAL MICE

1974 ◽  
Vol 140 (6) ◽  
pp. 1660-1675 ◽  
Author(s):  
Kathleen B. Bechtol ◽  
John H. Freed ◽  
Leonard A. Herzenberg ◽  
Hugh O. McDevitt
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Antibody Response ◽  
Genetic Control ◽  
Binding Capacity ◽  
High Responder ◽  
Total Serum ◽  
Antigen Binding ◽  
Low Responder

In order to further delineate the mechanisms underlying genetic unresponsiveness, tetraparental mice were constructed from immune response-1A gene high responder and low responder parental genotypes, then were immunized with poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys ((T,G)-A--L). An analysis of the total serum allotype mixture and of the antigen-binding capacity of the separated allotypes demonstrated that in the milieu of a tetraparental mouse, both high and low responder B cells could be stimulated equally to produce identical high titered anti-(T,G)-A--L responses. Furthermore, these studies show that effective stimulation could occur across a histocompatibility disparity.

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
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