Studies on the Effect of the Carrier Molecule on Antihapten Antibody Synthesis

Siskind, Gregory W.; Paul, William E.; Benacerraf, Baruj

doi:10.1084/jem.123.4.673

Cited by 57 publications

(31 citation statements)

References 23 publications

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“…However, from our work in presenting antigen in various forms and by different routes it is apparent that this mechanism is influenced by antigen-specific stimulants as has been shown previously by Siskind et al (1966), Liu et al (1974 and Moreno & Esdaile (1983).…”

Section: Discussionsupporting

confidence: 65%

The IgG Subclass Responses to Influenza Virus Haemagglutinin in the Mouse: Effect of Route of Inoculation

Hocart

Mackenzie²,

Stewart³

1989

Journal of General Virology

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SUMMARYThe influence of the route of infection, regime of inoculation and virus preparation on murine IgG subclass responses to the haemagglutinin of influenza A virus were examined. Virus preparations inoculated by the intraperitoneal, intravenous, intramuscular and intranasal routes were found to induce different IgG subclass profiles after a primary and secondary dose. IgG2a was found to be a major contributor to the responses elicited by all virus preparations irrespective of the route of inoculation. The magnitude of the response varied with the number of doses of virus and the route of inoculation; the intravenous and intramuscular routes produced the largest responses after two doses of virus. Evidence for the local production of antibody is presented and the influence of antigen presentation on the induction of different subclasses is discussed.

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Section: Discussionsupporting

confidence: 65%

The IgG Subclass Responses to Influenza Virus Haemagglutinin in the Mouse: Effect of Route of Inoculation

Hocart

Mackenzie²,

Stewart³

1989

Journal of General Virology

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“…These observations lead to conclusion that the nature of the protein carrier, to which each of the peptidyl groups is attached, strongly influences the capacity of the poly-DL-phenylalanyl determinant to inhibit the formation of anti-poly-DT.-alanyl antibodies. This resembles other phenomena in which the role of carrier has been demonstrated, such as the ability of haptenprotein conjugates to stimulate a secondary response in rabbits (20), the capacity to elicit delayed hypersensitivity reaction in sensitized gnineapigs (21,22), and the influence of the carrier on some properties of antibodies formed toward the same haptenic group (23,24).…”

Section: Discussionsupporting

confidence: 66%

Antigenic Competition Between Polypeptidyl Determinants in Normal and Tolerant Rabbits

Schechter

1968

The Journal of Experimental Medicine

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Competition between two polypeptidyl determinants was studied in normal rabbits and rabbits made tolerant to the competing antigen. The capacity of poly-DL-phenylalanyl protein conjugate to inhibit the formation of antibodies specific to the poly-DL-alanyl determinant was dependent on the nature of the protein carrier of the singly substituted antigens. Competition occurred only when the peptidyl determinants were attached to identical or similar (RSA and HSA) carriers. Thus, the immune response toward the poly-DL-alanyl determinant was impaired by injecting the pairs p-DL-PheRSA and p-DL-AlaHSA, or p-DL-PheRNase and p-DL-AlaRNase. Suppression of the formation of antibodies with poly-DL-alanyl specificity was not observed, however, upon administration of p-DL-PheRSA together with p-DL-AlaRNase or of p-DL-PheRNase with p-DL-AlaHSA. Tolerance to p-DL-PheRSA was induced by injecting this material into newborn rabbits. The tolerant animals retained their capacity to produce anti-poly-DL-alanyl antibodies upon injection of p-DL-AlaRSA or p-DL-AlaHSA. However, when these poly-DL-alanyl proteins were administered together with p-DL-PheRSA, antibodies against the poly-DL-alanyl determinant were not formed even though no antibodies with poly-DL-phenylalanyl specificity were produced. These results indicate that in competition experiments the preference in the immune response against a given determinant is dependent not only on the nature of the competing determinants, but it is also governed to a large extent by the over-all properties of the antigenic molecules. This suggests that at the stage at which the competition occurs the competing molecules had not undergone considerable degradation. On the basis of experiments with tolerant animals, it is suggested that in normal animals antibody formation to the competing antigen is not the cause of its inhibitory action on the response against the other antigen. The competition experiments described suggest that an antibody-forming cell is multipotent.

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“…

The dilemma in whicli we find ourselves iii relation to mechanisms of B cell activation illustrates well the limitations of the reductionist approach of conventional laboratory science (Bumet 1969). Any reasonably satisfying intellectual picture needs to encompass at least three problem streams: the entry, transport, trapping, retention and catabolism of antigen (Nossal & Ada 1971); the collaborative phenomena involving T cells, macrophages and B cells which are frequently required for activation (Miller 1972); and the elaborate events of B cell proliferation and differentiation underlying antibody production, immunological memory, germinal centre formation and affinity maturation (Siskind et al 1966). Furthermore, as we hope to show, activation ciinnot be understood without paying heed to the opposite option confronting the lymphocyte, namely tolerance, and this in turn needs to be seen in the context of B lymphocyte ontogeny (Nossal & Pike 1973, 1975.

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confidence: 99%