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 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 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

1973 ◽  
Vol 137 (5) ◽  
pp. 1180-1200 ◽  
Author(s):  
Günter J. Hämmerling ◽  
Tohru Masuda ◽  
Hugh O. McDevitt
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Immune Response Gene ◽  
Low Responders ◽  
Peripheral T Cells ◽  
Igg Receptors ◽  
Low Responder ◽  
Spleen And Lymph Nodes ◽  
Cell Defect

The influence of immunization with (T,G)-A--L on the frequency and characteristics of [125I] (T,G)-A--L-binding cells (ABC) was investigated in high and low responder mice, whose ability to respond to (T,G)-A--L is under control of an H-2-linked immune response gene, Ir-1. Unimmunized high and low responder mice have about the same number of ABC in spleen and lymph nodes (6–12 ABC/104). However, after immunization with (T,G)-A--L in aqueous solution, ABC in high responders increase to a much greater extent than they do in low responders. By inhibition of ABC with class-specific anti-Ig sera, it was demonstrated that in nonimmune and primed mice antigen is bound to IgM receptors, which is in agreement with the exclusive production of 19S anti-(T,G)-A--L antibody in primed animals. In contrast, after secondary challenge with antigen, ABC in high and low responder mice have mainly IgG receptors, although under the conditions used for immunization, low responders are not able to produce detectable amounts of 7S anti-(T,G)-A--L antibody. From these results and from the evidence that low responders very probably have a T cell defect, it is suggested that the switchover from IgM to IgG precursor cells can be induced by antigen itself, without the action of specific T cells. Furthermore, the failure of marked proliferation of ABC in low responders after antigenic stimulation is explained by the lack of stimulation by specific T cells. By independent methods it has been shown that all ABC detected in this study are B cells. Preliminary experiments indicate that purified peripheral T cells bind antigen, but much less per cell than do B 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 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 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 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 Immune Response of Indian Preterm Infants to Pentavalent Vaccine Varies With Component Antigens and Gestational Age

2021 ◽  
Vol 12 ◽  
Author(s):  
Archana Kulkarni-Munje ◽  
Nandini Malshe ◽  
Sonali Palkar ◽  
Aniket Amlekar ◽  
Sanjay Lalwani ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Antibody Response ◽  
Preterm Infants ◽  
Gestational Age ◽  
Childhood Vaccination ◽  
Pentavalent Vaccine

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.

scholarly journals H-2-linked control of cytotoxic T-cell responsiveness to alphavirus infection. Presence of H-2Dk during differentiation and stimulation converts stem cells of low responder genotype to T cells of responder phenotype.

1979 ◽  
Vol 149 (3) ◽  
pp. 786-790 ◽  
Author(s):  
A Mullbacher ◽  
R V Blanden
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Viral Antigen ◽  
Sindbis Virus ◽  
Fetal Liver ◽  
F1 Hybrids ◽  
Cytotoxic T Cell ◽  
Low Responder ◽  
Alphavirus Infection ◽  
High Responders

Secondary Tc cells generated against Sindbis virus (SIN) are restricted to Dk. All other H-2K or D regions tested show low specific responsiveness. F1 hybrids between low and high responders show dominance of responsiveness but lack complementation. When BALB/c (KdIdDd) low responder fetal liver stem cells were allowed to mature in irradiated high responder recipients C3H.OH (KdIdDk) a response to Dk plus SIN could be generated with Tc cells of BALB/c origin. This result, together with the failure of complementation in the F1 hybrids, implies that the lesion of low responsiveness is in the inability of viral antigen to stimulate a Tc-cell response in association with any self H-2K or H-2D molecule (of those tested) other than H-2Dk. Hypotheses compatible with these data are discussed.

scholarly journals THE IMMUNE RESPONSE AGAINST HAPTEN-AUTOLOGOUS PROTEIN CONJUGATES IN THE MOUSE

1973 ◽  
Vol 137 (4) ◽  
pp. 911-931 ◽  
Author(s):  
Bent Rubin ◽  
Hans Wigzell
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Serum Albumin ◽  
Cell Function ◽  
Cross Reactivity ◽  
Autologous Serum ◽  
Antigenic Determinants ◽  
Mouse Serum ◽  
Rat Serum

Mice immunized with hapten-autologous serum albumin conjugates (DNP-mouse serum albumin) were shown to contain immune B and T cells with specificity for the conjugate. Fractionation on antigen-coated Sepharose beads showed that B cells could be subdivided in two major groups: those reacting against the haptenic group (DNP) and those reactive against the new antigenic determinants (NADs) introduced into the protein carrier by the hapten coupling. It was shown previously that humoral antibodies formed against hapten-mouse serum albumin conjugates also were directed against these two groups of antigenic determinants and that the immune response to the NADs does not follow the genetic rules of high or low response against the hapten used. All together these findings support the distinct nature of the NADs over the haptenic groups, as recognized both at the humoral and cellular level. Absorption of mouse cells immune to hapten-autologous serum albumin conjugates on antigen-coated Sepharose beads using a variety of incubation conditions resulted in no specific retention of T cells. Therefore we had to resort to specificity studies of T cells in relation to T cell function. Relatively pure immune T cell suspensions were obtained using fractionation on anti-immunoglobulin-coated columns. DNP-MSA-specific T cells were shown to be very specific for the DNP-MSA conjugate with only one exception: they cross-reacted with antigenic determinants on DNP-rat serum albumin. As DNP-specific help was excluded in the present transfer system (as shown by the inability of cells from DNP-skin-painted mice and DNP-heterologous protein conjugate specific T cells [anti-immunoglobulin column purified] to help a DNP-MSA response), these results demonstrate the NAD specificity of the DNP-MSA-reactive T cells. The cross-reactivity pattern of DNP-MSA-specific T cells was similar to that found for humoral anti-NAD antibodies produced against the same immunogen. Whether B and T cells are activated by the same antigenic determinants is discussed.

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