Antigen Recognition Responsible for the Induction In Vitro of the Secondary Response

368

119

Rabbits primarily stimulated with a BSA (bovine serum albumin)-sulfanilic acid complex will produce a good secondary response to the sulfanilic acid hapten if the carrier used in the secondary stimulus is again BSA, and not if the secondary carrier is HGG (human gamma globulin). In the latter situation, a good secondary response is obtained, however, if the rabbits are pretreated a few weeks earlier with free HGG. We conclude that the immune stimulus involves the recognition of carrier determinants unrelated to the hapten. As the receptors for recognition of unrelated determinants are probably situated on different cells, we suggest that the immune stimulus leading to antibody formation requires the interaction of two antigen-bridged cells.

Section: Resultsmentioning

confidence: 61%

The Requirement of More Than One Antigenic Determinant for Immunogenicity

Rajewsky

Schirrmacher

Nase

et al. 1969

368

119

“…In other hapten-carrier systems, carrier specificity seems to be less pronounced (26)(27)(28)(29). Particularly relevant here are Mitchison's studies of the adoptive secondary response to hapten-protein conjugates in mice, where dose-response relationships were carefully established and evidence was presented that carrier specificity could be overridden by high doses of antigen (1,5,26). Several mechanisms can be envisioned which would resolve these discrepancies: (a) certain haptenic determinants may cooperate with each other whereas others may not, depending on the spectrum of specificities present on the helper cells (4); (b) for some or all antigens, dose ranges may exist, where precursor cells are induced without the need of cell cooperation (this may depend on the affinity to the antigen of the receptor molecules on the precursor cells) ; (c) in the normal in vivo situation, additional mechanisms pronouncing carrier specificity may exist which do not operate in the adoptive secondary response.…”

Section: Discussionmentioning

confidence: 99%

Determination of Antibody Class in a System of Cooperating Antigenic Determinants

Schirrmacher

Rajewsky

1970

19S and 7S memory is analyzed in a system of cooperating antigenic determinants. Cooperation occurs in the induction of both 19S and 7S secondary antibodies, and for both responses carrier specificity can be entirely accounted for by presensitization of the animal to carrier determinants. The class distribution of secondary anti-hapten antibody depends on the dose of the hapten primary-carrier conjugate used for priming, and on the time interval between priming with the hapten primary-carrier conjugate and secondary injection. The conditions of priming with the secondary carrier influence the extent of the secondary response but not the class distribution of secondary antibody. The data confirm the cooperation hypothesis of antibody induction. Specifically, we interpret them to mean that in hapten-carrier cooperation, the hapten-specific memory cells are predetermined for the class of the emerging antibodies. Together with the hapten-specific memory cells, the carrier-specific helpers are responsible for the extent of the secondary response.

“…The other cell fails to secrete detectable amounts of antibody, but nevertheless plays a role in the activation of the precursor described above (3,20,21). In the mouse, this "helper" cell has been demonstrated to be thymus-derived and to bear the isoantigen 0 (8,22).…”

Section: Discussionmentioning

confidence: 99%

Carrier Function in Anti-Hapten Antibody Responses

Katz

Paul

Goidl

et al. 1971

198

The studies reported here demonstrate that immunocompetent lymphoid cells from allogeneic donor guinea pigs stimulate the synthesis of anti-DNP and anti-OVA antibodies by recipients previously primed with DNP-OVA. This allogeneic effect occurs spontaneously in the absence of any further anti-genic challenge. Furthermore, the transfer of allogeneic cells prepares DNP-OVA-primed recipients for a striking secondary anti-DNP response to DNP-BGG; this occurs in equal degree whether or not the cells are derived from BGG-primed donors. We suggest that the allogeneic cells function by virtue of a specific immunologic attack of grafted cells on host cells. This conclusion is made on the basis of the following evidence: (a) The failure of observing the phenomenon with L2C leukemia cells and irradiated strain 2 lymph node and spleen cells which, although capable of initiating a host-versus-graft response, are incapable of mediating graft-versus-host reactions; and (b) the inability of (strain 2 x strain 13) F1 hybrids to mediate the allogeneic effect in strain 13 recipients. The analysis of this phenomenon may offer a key to the delineation of mechanisms involved in the activation of precursors of antibody-forming cells.