The Specificity of Allergic Reactions

215

A2G mice could be solidly immunized against the Ehrlich ascites tumor by single intraperitoneal injections of homogenized and lyophilized tumor cells which had been infected with oncolytic strains of influenza A virus. Similar homogenates from noninfected tumor cells were not immunogenic, even when mixed with egg-grown virus. The immunizing principle in viral oncolysates could not be separated from the oncolytic virus by differential centrifugation or adsorption to and elution from red cells. It could be inhibited by antibody raised in rabbits against the egg-grown oncolytic virus. This reaction showed serologic specificity. Thus, the immunogenicity of an oncolysate produced with the WSA strain of neurotropic influenza virus could be inhibited by rabbit anti-WSA, but not by rabbit antibody to the TUR strain of fowl plague virus. Conversely, the immunogenicity of an oncolysate prepared with the TUR strain could be inhibited by rabbit anti-TUR, but not by anti-WSA. When mice were preimmunized (primed) with egg-grown WSA virus, their antitumor response to a later injection of WSA oncolysate was of the anamnestic type. Priming with egg-grown influenza B virus had no such effect. It was concluded that the immunogenicity of certain host cell components was greatly increased by incorporation into the makeup of the oncolytic virus.

Section: Discussionmentioning

confidence: 99%

Viral Oncolysis: Increased Immunogenicity of Host Cell Antigen Associated With Influenza Virus

Lindenmann

Klein

1967

215

“…Establishment of Conditions to Alter T-Cell Responses to Adjacent Determinants on ABA-Protein Conjugates . The phenomenon of immunodominance of protein determinants in inducing delayed hypersensitivity after injection of hapten-protein conjugates has been recognized for many years (2,3) . Briefly, in the ABA-T system, it happens that whereas immunization of guinea pigs with ABA-T in CFA induces excellent ABA-specific delayed sensitivity, the administration of ABA coupled to a protein will not induce delayed sensitivity to ABA but will do so to determinants of the adjacent protein (4,5) .…”

Section: Failure Of Aba-specific Suppressor Cells To Inhibit T-cell Rmentioning

confidence: 99%

“…Thus, ABA-T is clearly less immunogenic for the elicitation of delayed hypersensitivity than the determinants of native proteins such as HGG since stimulation of delayed hypersensitivity to ABA-T requires immunization with CFA (4) whereas delayed sensitivity to foreign protein antigens can be observed after immunization by the appropriate route in either saline or IFA (2,3,15) . Furthermore, immunizations with ABA conjugates of immunogenic proteins always result in strong delayed hypersensitivity responses to the protein determinants and weak or absent ABA-specific responses.…”

Section: Failure Of Aba-specific Suppressor Cells To Inhibit T-cell Rmentioning

confidence: 99%

Induction of T-lymphocyte responses to a small molecular weight antigen. III. T-T cell interactions to determinants linked together: suppression vs. enhancement.

Bullock¹,

Katz²,

Benacerraf³

1975

The experiments presented in this paper demonstrate the existence of T-T cell interactions in responses to azobenzenearsonate (ABA)-protein conjugates, and also make the point that the spectrum of T-cell regulation from facilitation (i.e., help) at one end to suppression at the other, which has been well documented in T-B cell interactions, is also followed in T-cell regulation of other T lymphocytes. The data extend the activity of ABA-specific suppressor cells, which were shown to specifically suppress the development of delayed hypersensitivity to ABA-T, to T cells responsible for delayed hypersensitivity to protein antigens provided immunization is carried out with ABA conjugates of these antigens. Thus, suppressor T cells acting on the development of delayed hypersensitivity are not limited in their effects to T cells bearing the same specificity but can effectively suppress responses on immunologically unrelated T cells if they are specific for carrier antigens covalently linked to the ABA-T determinant. Moreover, these studies demonstrate that, as is true of T-B cell interactions, the most efficient T-T cell interactions occur to determinants linked together on the same molecule thus supporting the concept that development of effector T-cell function may involve participation of at least two distinct precursor cells, each of which may convey independent determinant specificities and/or genetic control.

“…According to this view, the energy that will allow binding of a sufficient amount of antigen to induce the immune response is only provided by adding the contribution of the carrier to the immunological specificity of the hapten. In support of this interpretation, there has been ample evidence for carrier specificity in hapten-protein and hapten-polypeptide systems for the reactions of actively sensitized cells with antigen such as delayed hypersensitivity (9,10,11) and anamnestic reactions (12). In the hapten-PLL system, an unequivocal example of antibody with carrier specificity has been reported in the case of anti-DNP-PLL antibodies produced by genetic responder guinea pigs.…”

mentioning

confidence: 94%

Cellular Localization of Anti-DNP-PLL and Anticonveyor Albumin Antibodies in Genetic Nonresponder Guinea Pigs Immunized With DNP-PLL Albumin Complexes

Green

Vassalli

Benacerraf

1967

About 30-40% of random-bred Hartley (I) and all strain 2 (2) guinea pigs recognize poly-L-lysine (PLL) I and hapten-PLL conjugates as antigens. These "responder" animals develop delayed hypersensitivity to the conjugated polymer and produce specific antihapten antibodies when immunized with hapten-PLL conjugates. The ability to respond to these antigens was shown to be controlled by a dominant autosomal gene (2, 3). Hapten-PLL conjugates which are complete antigens only for responder animals can behave as haptens in genetic nonresponder guinea pigs. Thus, insoluble electrostatic complexes formed by the reaction of positively charged 2,4-dinitrophenyl-PLL (DNP-PLL) with negatively charged foreign albumins, acting as conveyor or Schlepper molecules, induce the formation of high serum levels of anti-DNP antibodies in nonresponder guinea pigs (4). These animals, however, in contrast with responder guinea pigs, do not show delayed hypersensitivity reactions to DNP-PLL, which is not surprising, since it is well known that unconjugated haptens cannot elicit delayed hypersensitivity reaction (5). In these systems, the recognition of antigenicity and the capacity to show delayed hypersensitivity reactions therefore involve some identical immunological recognition mechanism in which the specificity of the carrier molecule plays an important part. This relationship is further illustrated by the observations of Schlossman on the ez DNP-oligo-L-lysines that the same minimum number of 7-8 lysine residues is essential both for immunization of responder guinea pigs and for the elicitafion of delayed hypersensitivity reactions in these animals (6, 7).An understanding of the immune response to hapten-protein and hapten-polypeptide conjugates must depend upon a better knowledge of the hapten-carrier rela-*