Studies on Artificial Antigens

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Hartley guinea pigs genetically unresponsive to hapten-PLL (poly-L-lysine) conjugates were lethally irradiated and given allogeneic bone marrow from Hartley responder animals. Many of the animals died of graft versus host disease before their response to 2,4-dinitrophenyl-PLL (DNP-PLL) could be measured. The immune response of the surviving recipient animals was evaluated by anti-DNP antibody production, development of delayed hypersensitivity to DNP-poly-L-lysine, as well as by lymph node cell stimulation in vitro by this antigen. 12 of 14 recipient animals thus treated made an immune response as measured by 2 of the 3 parameters. Strain 13 guinea pigs, genetically unable to respond immunologically to DNP-PLL and to DNP-GL (2,4-dinitrophenyl-L-glutamic acid L-lysine copolymer) were lethally irradiated and given bone marrow from (2 x 13) F1 responder animals or strain 13 bone marrow and (2 x 13) F1 lymph node and spleen cells. A high proportion of the animals survived this procedure; no evidence of graft versus host disease was observed. Three of three strain 13 animals irradiated and, given strain 13 bone marrow and (2 x 13) F1 lymph node and spleen, and then immunized with DNP-PL, made a specific immune response. 7 of 10 irradiated strain 13 animals given strain 13 bone marrow and (2 x 13) F1 lymph node and spleen made an immune response to DNP-GL. However, only one of six irradiated strain 13 animals made a vigorous immune response to DNP-GL after reconstitution with (2 x 13) F1 bone marrow alone. The ability to transfer the immune response to PLL antigens from responder to nonresponder animals demonstrates unequivocally that the defect in the non-responder animals is immunological rather than due to some other type of non-immunological mechanism. The bone marrow contains all the immunological cells necessary for the expression of the PLL gene. However, the finding that (2 x 13) F1 lymph node and spleen cells were more effective than (2 x 13)F1 bone marrow cell populations (known to be a rich source of monocyte precursors) suggests that the cells in which the PLL gene function is expressed may be lymphocytes rather than monocytes and macrophages.

Section: Discussionmentioning

confidence: 99%

Section: Tra~f~ Of Responsiveness To Dnp-pll To Lethally Irrad~t~ Rarmentioning

confidence: 99%

Section: (From the Laboratory Of Immunology National Institute Of Almentioning

confidence: 99%

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TRANSFER OF RESPONSIVENESS TO HAPTEN CONJUGATES OF POLY-L-LYSINE AND OF A COPOLYMER OF L-GLUTAMIC ACID AND L-LYSINE TO LETHALLY IRRADIATED NON-RESPONDER GUINEA PIGS BY BONE MARROW OR LYMPH NODE AND SPLEEN CELLS FROM RESPONDER GUINEA PIGS

Foerster

Green

Lamelin

et al. 1969

Self Cite

“…DNP3-GL was prepared by the reaction of 2,4-dinitrofluorobenzene with GL (12). The subscript refers to the average number of DNP groups per molecule.…”

Section: Methodsmentioning

confidence: 99%

Function of Macrophages in Antigen Recognition by Guinea Pig T Lymphocytes

Shevach

Rosenthal

1973

502

Recent studies indicate that histocompatibillty-linked immune response (It) 1 genes, are expressed on thymus-derived (T) lymphocytes. In the mouse, the genetically controlled difference in the IgG antibody response between high and low responders immunized with branched-chain amino acid polymers is lost in thymus-deprived mice (1). In guinea pigs, the initiation of functions thougtrt to be regulated by T lymphocytes (delayed cutaneous hypersensitivity, antigen-induced lymphocyte proliferation in vitro, and carrier function) requires the presence of the appropriate Ir gene (2). Thus, guinea pigs that lack the poly-L-lysine (PLL) gene (nonresponders) fail to develop either delayed hypersensitivity or other cellular immune phenomena upon immunization with 2,4-dinitrophenyl (DNP)-poly-L-lysine. Nonetheless, these animals are capable of recognizing DNP-PLL as a hapten and produce antibodies to DNP-PLL when this molecule is coupled to an immunogenic protein carrier (3). In addition, recent data indicate that the number of specific antigen-binding bone marrow-derived (B) lymphocytes does not differ between responders and nonresponders (4-6). Schlossman (7) has also recently shown that the antibody clones and the variable region gene pool for antibodies to a-DNP-deca-L-lysine, an antigen the response to which is controlled by the PLL gene, appear to be indentical in responder and nonresponder animals. Thus, the weight of experimental evidence suggests that the main functional role of the Ir gene product is in the process of antigen recognition by the T lymphocyte.However, an alternative explanation to these studies is that the Ir genes might be expressed in a cell that controls and regulates T-cell activation, i.e., the macrophage. A number of attempts have been made to resolve this issue by using cell transfer studies (8, 9). When spleen and lymph node cells were transferred from (2 X 13)F1 animals to lethally irradiated strain 13 guinea pigs that had been reconstituted with syngeneic bone marrow, a large percentage of the recipients developed the ability to respond to antigens controlled by the PLL gene; lethally irradiated strain 13 guinea 1 Abbreviations used in this paper: DNP, 2,4-dinitrophenyl; GL, a copolymer of L-glutamic acid and L-lysine; GT, a copolymer of L-glutarnic acid and L-tyrosine; It, immune response; LNL, lymph node lymphocytes; NGPS, normal guinea pig serum; PEC, peritoneal exudate cells; PELs, peritoneal exudate lymphocytes; PHA, phytohemagglutinin; PLL, poly-L-lysine; PPD, purified protein derivative of tuberculin.

“…PLL responder guinea pigs develop delayed hypersensitivity, a T-cell function (9), to the PLL antigen. PLL nonresponders do not develop delayed hypersensitivity to PLL (10). When responder and nonresponder guinea pigs are immunized with DNP-PLL, only responder animals produce detectable anti-DNP antibody.…”

mentioning

confidence: 99%

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

Bechtol

Freed

Herzenberg

et al. 1974

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.