The Requirement of More Than One Antigenic Determinant for Immunogenicity

Rajewsky, Klaus; Schirrmacher, Volker; Nase, S.; Jerne, Niels K.

doi:10.1084/jem.129.6.1131

Cited by 368 publications

(126 citation statements)

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“…The number of plaque-forming cells (PFC) in the draining lymph nodes and the serum antibody levels were measured [10][11]18, and 30-33 days after DNP-GPA immunization. In addition, the avidity of antibody secreted by PFC was measured by a hapten-inhibition technique which allows the enumeration of PFC producing antibody of any given avidity (14).…”

mentioning

confidence: 99%

Hapten-Specific Tolerance

Davie

Paul

Katz

et al. 1972

The Journal of Experimental Medicine

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The treatment of guinea pigs with 2,4-dinitrophenyl (DNP) t derivatives of the copolymer of D-glutamic acid and D-lysine (D-GL) induces a state of specific immunologic tolerance in the recipient (1). The type of tolerance induced is unusual in that it is DNP specific. That is, challenge of such guinea pigs with a DNP conjugate of ovalbumin (DNP-OVA) elicits anti-DNP responses markedly smaller than those of animals which have not been pretreated with DNP-B-GL. The degree of depression in responsiveness is related to the dose of tolerogen, to the mode of immunization with DNP-OVA, and to the interval between the two events. A similar type of haptenspecific tolerance, in mice, has recently been described by both Hraba et al. (2) and by Golan and Borel (3).The tolerant state, in this model, appears to be largely expressed in the precursors of antibody-secreting cells. The evidence for this view is the following:(a) The number of DNP-specific antigen-binding lymphocytes in the lymph nodes of tolerized animals is markedly reduced (1). These antigen-binding lymphocytes are members of the bone marrow-derived (B) lymphocyte pool and include the precursors of antibody-secreting cells (4).(b) The tolerance is hapten specific (1). Thymus-derived (T) lymphocytes acting as "helpers" in the activation of precursor cells are almost exclusively carrier or conjugate specific (5, 6); on the other hand, hapten-specific precursors of antibodysecreting cells are relatively common (4, 7). Hapten-specific tolerance thus implies precursor cell tolerance.(c) Even when an excess of helper cells are provided through an immunization with carrier after tolerance induction with DNP-D-GL but before challenge with DNPcarrier conjugate, the subsequent anti-DNP response is markedly diminished (1). Thus, in a situation in which helper T cells are not limiting, the hapten-specific tolerance is easily demonstrable, again implying a defect in the population of precursors of antibody-secreting cells.

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confidence: 99%

Hapten-Specific Tolerance

Davie

Paul

Katz

et al. 1972

The Journal of Experimental Medicine

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“…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: 81%

“…Indeed, the use of complete Freund's adjuvant for sensitization in the studies on the carrier effect induces DH to the carrier (13,16,17). 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).…”

Section: Discussionmentioning

confidence: 99%

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Immunodeviation by Passive Antibody, an Expression of Selective Immunodepression

Vuagnat

Neveu

Voisin

1973

The Journal of Experimental Medicine

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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.

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“…which are the antibody producers [3,4,12]. In our experimental system, the low-responder C57BL/6 mice produced anti-hapten antibody after a primary immunization with trinitrophenylated (TNP) sheep erythrocytes (SRBC), but not after an immunization with TNP-HRBC [11].…”

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confidence: 99%