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.

scholarly journals Genetic control of the immune response to staphylococcal nuclease. IV. H-2-linked control of the relative proportions of antibodies produced to different determinants of native nuclease.

1977 ◽  
Vol 145 (1) ◽  
pp. 123-135 ◽  
Author(s):  
J A Berzofsky ◽  
A N Schechter ◽  
G M Shearer ◽  
D H Sachs
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Antibody Response ◽  
Binding Capacity ◽  
Staphylococcal Nuclease ◽  
Gene Control ◽  
Low Responder ◽  
Selection Of ◽  
Ir Genes

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.

scholarly journals ANTIGEN-SPECIFIC THYMUS CELL FACTORS IN THE GENETIC CONTROL OF THE IMMUNE RESPONSE TO POLY-(TYROSYL, GLUTAMYL)-POLY-D, L-ALANYL--POLY-LYSYL

1974 ◽  
Vol 140 (2) ◽  
pp. 301-312 ◽  
Author(s):  
M. J. Taussig ◽  
Edna Mozes ◽  
Ronit Isac
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
Genetic Control ◽  
Bone Marrow Cells ◽  
High Responder ◽  
Low Responder

The genetic control of the antibody response to a synthetic polypeptide antigen designated poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(T, G)-A--L] has been studied in congenic high responder C3H.SW (H-2b) and low responder C3H/HeJ (H-2k) strains of mice. This response is controlled by the Ir-1 gene and is H-2 linked. The method employed was to study the ability of specifically primed or "educated" T cells of each strain to produce cooperative factors for (T, G)-A--L in vitro. Such factors have been shown to be capable of replacing the requirement for T cells in the thymus-dependent antibody response to (T, G)-A--L in vivo. The T-cell factors produced were tested for their ability to cooperate with B cells of either high or low responder origin by transfer together with bone marrow cells and (T, G)-A--L into heavily irradiated, syngeneic (for bone marrow donor) recipients. Direct anti-(T, G)-A--L plaque-forming cells were measured later in the spleens of the recipients. The results showed that (a) educated T cells of both high and low responder origin produced active cooperative factors to (T, G)-A--L, and no differences between the strains in respect to production of T-cell factors could be demonstrated; and (b) such factors, whether of high or low responder origin, cooperated efficiently with B cells of high responder origin only, and hardly at all with B cells of low responder origin. The conclusion was drawn that the cellular difference between the two strains lies in the responsiveness of their B cells to specific signals or stimuli received from T cells. As far as could be discerned by the methods used, no T-cell defect existed in low responder mice and the expression of the controlling Ir-1 gene was solely at the level of the B cells in this case.

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 The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody

1978 ◽  
Vol 147 (6) ◽  
pp. 1849-1853 ◽  
Author(s):  
CM Warner ◽  
TJ Berntson ◽  
L Eakley ◽  
JL McIvor ◽  
RC Newton
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Glutamic Acid ◽  
Gamma Globulin ◽  
High Responder ◽  
Gene Control ◽  
Low Responder ◽  
Bone Marrow Chimeras

The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder × high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.

scholarly journals Antibody response of C3H in equilibrium (CKB X CWB)F1 tetraparental mice to poly-L(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys immunization.

1976 ◽  
Vol 144 (1) ◽  
pp. 123-144 ◽  
Author(s):  
K B Bechtol ◽  
H O McDevitt
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
High Responder ◽  
Low Responders ◽  
First Case ◽  
Low Responder ◽  
Specific Stimulation ◽  
Stimulation Of

To test whether the antigen-specific stimulation of low responder-genotype B cells in tetraparental mice is due to a histoincompatibility reaction (allogeneic effect) against these B cells, tetraparental mice were constructed (a) between an Ir-1A low responder to the antigen poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys. [(T,G)-A--L] and an Ir-1A F1 high responder and (b) between two histoincompatible Ir-lA low responders. In the first case the F1 high responder embryo shares the whole of the H-2 complex, including Ir, with the low responder embryo.

scholarly journals GENETIC CONTROL OF THE ANTIBODY RESPONSE

1965 ◽  
Vol 122 (3) ◽  
pp. 517-531 ◽  
Author(s):  
Hugh O. McDevitt ◽  
Michael Sela
Keyword(s):  
Bovine Serum Albumin ◽  
Antibody Response ◽  
Genetic Control ◽  
Bovine Serum ◽  
Antigenic Determinant ◽  
Genetic Factor ◽  
Binding Capacity ◽  
Antigen Binding ◽  
Modifying Factors ◽  
Synthetic Polypeptide

Immunization of CBA and C57 mice with a branched, multichain synthetic polypeptide, poly (tyr,glu)-poly DL-ala--poly lys, ((T,G)-A--L), in Freund's complete adjuvant results in a tenfold or more difference in the antigen-binding capacity of sera from the two strains, although they respond equally to bovine serum albumin. Immunization of CBA x C57 F1, F1 x CBA, and F1 x C57 mice reveals definite genetic control of the response to (T,G)-A--L, which appears to be due to a single major genetic factor, with perhaps one or more modifying factors. Immunization of CBA and C57 mice with (H,G)-A--L, a synthetic polypeptide in which histidine replaces tyrosine, gives the opposite result, CBA's respond and C57's do not. From this, it appears that the genetic control of the response to (T,G)-A--L is specific for the antigenic determinant. The implications of these results are discussed.

scholarly journals Antigen-specific T-cell factors in the genetic control of the immune response to poly(Tyr,Glu)-polyDLAla--polyLys. Evidence for T- and B-cell defects in SJL mice.

1975 ◽  
Vol 141 (3) ◽  
pp. 703-707 ◽  
Author(s):  
E Mozes ◽  
R Isac ◽  
M J Taussig
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cell ◽  
Genetic Control ◽  
Bone Marrow Cells ◽  
High Responder ◽  
Specific Factor ◽  
Low Responder ◽  
Marrow Cells

The cellular basis of the genetic control of the immune response to poly(LTyr, LGlu)-polyDLAla--polyLLys [(T,G)-A--L] in SJL (H-2s, low responder) mice has been investigated using T-cell factors. Thymocytes of SJL origin were educated to (T,G)-A--L and tested for their ability to produce an antigen-specific factor capable of cooperating in vivo with bone marrow cells of either SJL or C3H.SW (high responder) origin. SJL T cells were found to be incapable of producing such a cooperative factor, in contrast with results previously obtained with C3H/HeJ (low responders) and C3H.SW strains. Moreover, SJL bone marrow cells did not produce an antibody response to (T,G)-A--L, even when combined with factor produced by high responder (C3H.SW) mice. Thus, both T and B cells appear to be defective in the SJL strain in the response to (T,G)-A--L.

scholarly journals Genetic control of immune response to myoglobin. Ir gene function in genetic restriction between T and B lymphocytes.

1982 ◽  
Vol 156 (5) ◽  
pp. 1486-1501 ◽  
Author(s):  
Y Kohno ◽  
J A Berzofsky
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
High Responder ◽  
Gene Control ◽  
Gene Defect ◽  
Genetic Restriction ◽  
Low Responder

We studied the genetic restrictions on the interaction between T cells, B cells, and antigen-presenting cells (APC) involved in the H-2-linked Ir gene control of the in vitro secondary antibody response to sperm whale myoglobin (Mb) in mice. The B cells in this study were specific for Mb itself, rather than for a hapten unrelated to the Ir gene control, as in many previous studies. Low responder mice immunized in vivo with Mb bound to an immunogenic carrier, fowl gamma globulin (F gamma G), produced B cells competent to secrete anti-Mb antibodies in vitro if they received F gamma G-specific T cell help. However, (high-responder X low responder) F1 T cells from Mb-immune mice did not help these primed low responder (H-2k or H-2b) B cells in vitro, even in the presence of various numbers of F1 APC that were demonstrated to be component to reconstitute the response of spleen cells depleted by APC. Similar results were obtained with B6 leads to B6D2F1 radiation bone marrow chimeras. Genotypic low responder (H-2b) T cells from these mice helped Mb-primed B6D2F1B cells plus APC, but did not help syngeneic chimeric H-2b B cells, even in the presence of F1 APC. In contrast, we could not detect any Ir restriction on APC function during these in vitro secondary responses. Moreover, in the preceding paper, we found that low responder mice neonatally tolerized to higher responder H-2 had competent Mb-specific helper T cells capable of helping high responder but not low responder B cells and APC. Therefore, although function Mb-specific T cells and B cells both exist in low responder mice, the Ir gene defect is a manifestation of the failure of syngeneic collaboration between these two cell types. This genetic restriction on the interaction between T cells and B cells is consistent with the additional new finding that Lyb-5-negative B cells are a major participant in ths vitro secondary response because it is this Lyb-5-negative subpopulation of B cells that have recently been shown to require genetically restricted help. The Ir gene defect behaves operationally as a failure of low responder B cells to receive help from any source of Mb-specific T cells either high responder, low responder, or F1. The possible additional role of T cell-APC interactions, either during primary immunization in vivo or in the secondary culture is discussed.

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 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.

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