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

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.

1970 ◽  
Vol 132 (4) ◽  
pp. 613-622 ◽  
Author(s):  
Edna Mozes ◽  
G. M. Shearer ◽  
Michael Sela

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.


1974 ◽  
Vol 140 (2) ◽  
pp. 349-355 ◽  
Author(s):  
Edna Mozes ◽  
Michal Schwartz ◽  
Michael Sela

Five inbred mouse strains which represent high and low responders to the random synthetic polypeptide poly(LTyr,LGlu)-polyDLAla--polyLLys, designated (T, G)-A--L, to which the immune response is controlled by an H-2-linked gene, were immunized with three ordered tetrapeptides composed of tyrosine and glutamic acid attached either to multichain poly-DL-alanine or to polyproline. Only one of the three antigenic determinants, namely tyrosyl-tyrosyl-glytamyl-glutamic acid (T-T-G-G), resembled the random peptide (T, G) in the pattern of immune responses elicited against it, and in the cross-reactivity of the specific antibodies with (T, G)-A--L. The immune response pattern to the other two ordered tetrapeptides, T-G-T-G and G-T-T-G, was different from that obtained with (T, G)-A--L, and no cross-reactivity was detected between the antibodies provoked with these peptides and (T, G)-A--L. Thus, it is suggested that T-T-G-G is a major determinant in the random (T, G)-A--L.


1980 ◽  
Vol 58 (12) ◽  
pp. 1405-1413 ◽  
Author(s):  
Phyllis R. Strauss ◽  
James M. Sheehan ◽  
Judith Taylor

In this paper we characterize the thymidine transport systems in nonadherent spleen cells from normal leukemic (AKR) mice and from AKR mice which have been stimulated in vivo with concanavalin A (Con A). We have shown that splenic lymphocytes from normal AKR mice transport thymidine (two kinetic components, Km values of 34 μM and 1.6 mM) whereas lymphoid cells from C57L/J and outbred (CD-1) mice do not. Following Con A stimulation of AKR mice, three components (Km values of 6 μM, 212 μM, and millimolar range) were observed. The current data should be compared with previously published results for splenocytes from Con A stimulated CD-1 mice. Although those cells transport thymidine with two kinetic components (Km values of 160 μM and 4 mM), they lacked the lowest Km system present in AKR splenocytes.Thymidine transport was also examined in lymphocytes from several AK × L recombinant inbred mouse strains derived from the cross AKR/J × C57L/J. Two strains which lacked MuLV did not show time-dependent thymidine translocation whereas two strains which possessed MuLV demonstrated time-dependent thymidine translocation. Moreover, cells from the congenic strain L.AKR-Akv-2, which carried the Akv-2 genome on a C57L background, also showed thymidine transport. Thus a unique ability to transport thymidine can be correlated with the presence of the murine leukemia virus genome.


2018 ◽  
Vol 17 (2) ◽  
pp. 317
Author(s):  
ADILSON RICKEN SCHUELTER ◽  
MAYARA FABIANA SILVA ◽  
JONATAS MARCOLIN ◽  
IVAN SCHUSTER ◽  
ISABEL PRAZERES DE SOUZA

 RESUMO - As plantas daninhas constituem um dos fatores que reduzem a produtividade do milho e, portanto, é importante conhecer o mecanismo de tolerância da cultura aos herbicidas, de forma a fornecer informações que minimizem os riscos de danos aos cultivos. Dessa forma, o objetivo do trabalho foi avaliar a resposta de linhagens de milho e o controle genético envolvido na tolerância aos herbicidas nicosulfuron e tembotrione. Duzentas e cinco linhagens de milho foram avaliadas quanto à reação aos herbicidas. Para a avaliação do controle genético de tolerância aos herbicidas foram empregadas duas linhagens tolerantes e duas sensíveis, as quais foram intercruzadas empregando um dialelo de meia tabela. As linhagens e as populações oriundas desses cruzamentos foram avaliadas quanto à reação aos herbicidas em delineamento de blocos casualizados com quatro repetições. As dosagens foram de 60 g ha-1 de nicosulfuron (Sanson®) e 100 g ha-1 de tembotrione (Soberan®). A avaliação fenotípica constituiu-se de número de plantas sensíveis e/ou tolerantes e o teste do Qui-quadrado (χ2) foi utilizado nas análises. Quanto à resposta à aplicação dos agroquímicos verificaram-se linhagens tolerantes ou sensíveis a ambos os herbicidas ou apenas a um deles. Nas avaliações do controle genético, as análises evidenciaram um gene com dominância completa que, pela análise de segregação das famílias F3, permitiu levantar a hipótese de genes fortemente ligados ou pleiotrópicos. Os resultados obtidos, associados ao retrocruzamento assistido por marcadores moleculares (RCAM), auxiliaram o processo de introgressão da tolerância nas linhagens sensíveis aos herbicidas nicosulfuron e tembotrione.Palavras-chave: Zea mays L., herança, melhoramento genético, marcadores moleculares.GENETIC TOLERANCE OF MAIZE LINES TO TEMBOTRIONE AND NICOSULFURON ABSTRACT - As weeds are one of the factors that reduce maize productivity it is important to know the mechanism of crop tolerance to herbicide in order to minimize the risk of damage to the plants. Thus, the objective of this work was to evaluate the response of maize inbred lines and the genetic control of the tolerance to the herbicides nicosulfuron and tembotrione. Two hundred and five maize inbred lines were evaluated for herbicides reaction. For the evaluation of the genetic control of tolerance to herbicides, two tolerant and two sensitive inbred lines were used, which were intercrossed using a half diallel table. The inbred lines and the populations obtained from these crosses were evaluated for reaction to the herbicides in a randomized complete block design with 4 replicates. The dosages were 60 g ha-1 of nicosulfuron (Sanson™) and 100 g ha-1 of tembotrione (Soberan™). The phenotypic evaluation was based on the number of sensitive and / or tolerant plants and the chi-square test (χ2) was used in the analysis. Regarding the response to the application of the agrochemicals, inbred lines were tolerant or sensitive to one or both herbicides. The analysis of genetic control showed a gene with complete dominance, and the segregation analysis of the F3 families hypothesized the occurrence of strongly linked or pleiotropic genes. The data obtained associated to marker-assisted backcrossing allowed the tolerance introgression in sensitive inbred lines to nicosulfuron and tembotrione.Keywords: Zea mays L., inheritance, plant breeding, molecular markers.


1979 ◽  
Vol 149 (6) ◽  
pp. 1407-1423 ◽  
Author(s):  
G M Shearer ◽  
A M Schmitt-Verhulst ◽  
C B Pettinelli ◽  
M W Miller ◽  
P E Gilheany

Spleen cells from B10.BR and C57BL/10 (B10) mice were compared for their ability to generate primary in vitro cytotoxic responses to syngeneic cells modified with different concentrations (from 10 to 0.031 mM) of trinitrobenzene sulfonate (TNBS) (TNP-self). Although both strains generated effector cells to TNP-self in the range of 10-0.25 mM TNBS modification, effector activity of B10 cells was weaker than that of B10.BR cells. B10 spleen cells did not respond to syngeneic stimulating cells modified at 0.1 mM or lower, whereas B10.BR cells generated effector activity even when stimulated by TNP-self modified with as low as 0.031 mM TNBS. Fluorescence analysis of the modified cells using the FACS II indicated that equivalent quantities of TNP were conjugated to the surfaces of B10.BR and B10 spleen cells for any given concentration of TNBS modification. Similar strain-dependent differences were observed when the TNP was diluted out in the cultures by reducing the number of stimulating cells modified with 10 mM TNBS. These response patterns were verified by stimulating cultures of B10.BR and B10 spleen cells either with TNP conjugated to bovine serum albumin or bovine gamma globulin (B10.BR but not B10 cells responded to TNP-conjugated proteins) or with TNBS-modified glass-adherent spleen cells. The strain-dependent differences could also be detected at the effector phase, because optimally stimulated B10.BR, but not B10 effector cells, could lyse 0.1 mM TNBS-modified syngeneic target cells. The genetic parameters associated with the response and nonresponse patterns of B10.BR and B10 mice were further investigated by comparing the cytotoxic responses to low doses of TNP-self of spleen cells from the following strains: (a) C3H/HeJ (H-2k) and C3H.SW (H-2b); (b) BALB.K (H-2k) and BALb.b (h-2b); and (c) B10.A (H-2a) and B10.D2 (H-2d). The H-2k and H-2a, but not the H-2b and H-2d, strains generated cytotoxic responses to TNP-self when the syngeneic stimulators were modified with 0.1 mM TNBS. Further studies using (B10 X B10.BR)F1 responding cells and parental or F1-modified stimulating cells, indicated that the F1 cells generated cytotoxic activity to low doses of TNP in association with H-2k but not in association with H-2b self products. The results of this study indicate that H-2-linked genetic factors, expressed in the target as well as in the responding and/or stimulating cell populations, control the ability of inbred mouse strains to generate cytotoxic effector cells to low doses of TNP-self. Such dose-dependent genetic effects may be important in the regulation of immune responses activated in vivo by chronic exposure to infectious agents.


2011 ◽  
Vol 13 (2) ◽  
pp. 155-163 ◽  
Author(s):  
A Laroque ◽  
G Min-Oo ◽  
M Tam ◽  
I Radovanovic ◽  
M M Stevenson ◽  
...  

2014 ◽  
Vol 193 (9) ◽  
pp. 4485-4496 ◽  
Author(s):  
Sara Mostafavi ◽  
Adriana Ortiz-Lopez ◽  
Molly A. Bogue ◽  
Kimie Hattori ◽  
Cristina Pop ◽  
...  

1972 ◽  
Vol 135 (6) ◽  
pp. 1259-1278 ◽  
Author(s):  
Hugh O. McDevitt ◽  
Beverly D. Deak ◽  
Donald C. Shreffler ◽  
Jan Klein ◽  
Jack H. Stimpfling ◽  
...  

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.


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