The Immune Response of Guinea Pigs to Hapten-poly-L-Lysine Conjugates as an Example of the Genetic Control of the Recognition of Antigenicity

105

A marked enhancement of anti-hapten antibody synthesis in response to immunization with a hapten-protein conjugate occurs as a result of pre-immunization of animals with unmodified carrier. This is true both for primary and secondary antihapten responses and is most strikingly demonstrated when an animal which has received a primary immunization with a hapten conjugate of a given carrier is boosted with the same hapten conjugated to a different carrier, to which the animal has been preimmunized (1-6).This phenomenon indicates the existence of independent recognition units for hapten and for carrier. Cooperative interaction between these units may be essential to the production of an anti-hapten antibody response, or may amplify a modest immune response which occurs in the absence of carrier-specific recognition.An understanding of the nature of the carrier recognition unit and of the range of substances which it recognizes and acts upon is required in order to construct a coherent picture of cooperative interactions in the immune response. Studies presented both by Mitchison and Rajewsky, et al. (4,5) and those reported in the first paper of this series (6) show that humoral antibody is not the carrier recognition unit.In the adoptive secondary antibody response in mice, hapten-carrier cooperative interactions appear to be mediated by hapten-specific and carrier-specific lymphoid cells (4, 7). In the present communication we show that live lymphoid cells from strain 2 guinea pigs immunized to bovine gamma globulin (BGG) enable syngeneic animals immunized with 2,4-dinitrophenyl ovalbumin (DNP-OVA) to form a secondary anti-DNP response to DNP-BGG. Thus, in both species the carrier recognition unit appears to be associated with a lympboid cell.Several relevant questions may then be asked concerning the significance of this phenomenon and the mechanism by which carrier-specific cells enhance anti-hapten antibody response. One suggested function of the carrier-specific cell is the concentration and presentation of antigen (4, 7). Such cells would bind multideterminant antigens by one of their determinants and simply present other determinants to appropriate hapten-specific cells ill certain anatomical locations. However, the possibility must also be considered that 283 on

Section: Ability Of Bgg-s Pecific Lymphoid Cells To Prepare Dn P-o V mentioning

confidence: 99%

Carrier Function in Anti-Hapten Immune Responses

Paul

Katz

Goidl

et al. 1970

105

“…(Received for publication 14 July 1969) The immune response of guinea pigs to poly-L-lysine (PLL) 1 and hapten conjugates of this polymer is predicated upon the presence of an autosomal dominant gene which is referred to as the "PLL gene" (1)(2)(3). This same gene also determines the immune response of guinea pigs to a copolymer of L-lysine and l~-giutamic acid (GL) and its hapten conjugates, although no cross-reactivity could be detected between anfi-GL and anti-2,4-dinitrophenyl PLL (DNP-PLL) antibodies (4).…”

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

confidence: 99%

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

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.

“…Carrier and hapten determinants are unrelated, separate determinants (14, 17); this conclusion is strongly favored by experiments where tolerance to the carrier reduces the response to the hapten (13,18,19). Carrier and hapten determinants must be on the same molecule (14,17,20), although recent reports challenge this conclusion (21)(22)(23)(24).…”

Section: Discussionmentioning

confidence: 80%

Immunodeviation by Passive Antibody, an Expression of Selective Immunodepression

Vuagnat

Neveu

Voisin

1973

The effect of passively administered IgG1 and IgG2 anticarrier antibodies on the IgG1 and IgG2 antihapten response has been studied. Guinea pigs were immunized with dinitrophenylated bovine gamma globulin mixed with purified IgG1 or IgG2 antihuman gamma globulin antibodies, i.e., antibodies directed against a limited range of the carrier determinants. Humoral IgG1 and IgG2 anti-DNP antibody contents were assayed at weekly intervals and 4 to 10 days after a booster injection of antigen in saline given on the 12th wk. The main finding was the sustained suppressive effect of passive IgG1 anti-carrier antibodies on the active IgG1 antihapten response. This result is compared with the enhancing effect of passive IgG1 antihapten antibodies and is discussed in the light of T cell-B cell and hapten-carrier relationships, leading to the proposal of a regulatory function of the Fc portion of the IgG1 anticarrier antibody, combined with the antigen, on the T cell.