Quantitative studies on antigenic recognition. II. Kinetics of the recognition event

Ramseier, H.

doi:10.1002/eji.1830010306

Cited by 16 publications

(19 citation statements)

References 20 publications

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“…Parental strain cells are the active partner endowed with the ability to recognize foreign antigens (8,9). Transplantation antigens were offered to these aggressor ceils in the form of appropriate F 1 hybrid spleen cells, called target cells.…”

Section: Product Of Antigenic Recognition (Par) Assay--this Test Wasmentioning

confidence: 99%

Cellular Receptors

Ramseier

Lindenmann

1971

The Journal of Experimental Medicine

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The injection of parental strain lymphoid cells into F1 hybrid animals is known to lead to manifestations of graft-versus-host (GVH) 1 reactions. It is generally agreed that the initiation of this process is set in motion by parental strain cells recognizing transplantation antigens the F1 host has inherited from the other parent (1). This recognition process is assumed to be accomplished by recognition structures (RS) presumably located on the surface of parental strain lymphoid cells. If such a parent-to-F1 GVH reaction is considered from a genetical point of view, it seems reasonable to assume that an F1 animal fails to detect on injected parental strain lymphoid cells any foreignness, with the notable exception of particular recognition structures.It was demonstrated earlier (2-4) that these structures were antigenic. The injection of moderate numbers of parental strain immunocompetent cells into F1 hosts led to the production of anti-recognition structure (anti-RS) antisera. The activity of these sera could be demonstrated by their ability to block the corresponding recognition structures on parental strain cells and thus prevent antigenic recognition. Anti-RS sera have, furthermore, been shown to be of exquisite specificity. Since for genetic reasons an F1 host can be expected to react only against RS which it does not possess, its serum will contain only antibody to the newly introduced parental RS. It could be shown that treatment of a suspension of parental strain lymphoid cells with such an antiserum blocked the RS in question but left RS for other transplantation antigens free to recognize corresponding antigens (3, 4).While these anti-RS sera have all been provoked by injections of low numbers of parental strain lymphoid cells into adult F~ hybrid hosts, the present communication intends to show that similar antibodies can be elicited by a seemingly remote immunization procedure. Instead of considering only immunocompetent cells as bearers of recognition structures for foreign trans-

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Section: Product Of Antigenic Recognition (Par) Assay--this Test Wasmentioning

confidence: 99%

Cellular Receptors

Ramseier

Lindenmann

1971

The Journal of Experimental Medicine

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“…The kinetics of PAR formation as observed in uninhibited cultures bore many similarities to that observed by simply mixing parental and F, spleen cells [22]. Thus, the time interval necessary to reach peak amounts and formation of PAR inhibitor were alike.…”

Section: Discussionmentioning

confidence: 57%

“…As noted before, untreated C57BL/6 cells having a normal set of receptors for CBA alloantigens [RS(CBA)] formed PAR together with CBA alloantigens [22], with peak amounts after 4 h of cultivation with (C57BL/6 x CBA)F, spleen cells. Decline of PAR activity was described earlier as due to the formation of a PAR inhibitor [22,26]. Temporarily RS(CBA)-less C57BL/6 spleen cells failed to form PAR with alloantigen CBA for the first 8 h of cultiva tion, but from 9 h on PAR could be discerned and peak amounts were formed 5 h later.…”

Section: Resynthesis Of T-cell Receptors For Alloantigen In Presence mentioning

confidence: 99%

Transplantation Tolerance at the T-Lymphocyte Receptor Level II.

Ramseier¹

1976

Pathobiology

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CBA T lymphocytes deprived temporarily of receptors for alloantigens A[RS(A)] cultivated in vitro for 30 h with anti-receptor antibody-forming (AxCBA)F₁ spleen cells were capable of resynthesizing RS(A) if primed F₁ cells exceeded parental T cells by a factor of 25 or less, but not if the excess was 50-fold or more. This indicated that resynthesis of CBA T-cell RS(A) was successful if primed F₁ cells formed insufficient amounts of anti-CBA T-cell RS(A) antibody. Abortive or successful receptor resynthesis was measured by two parameters, (a) reappearing RS(A) formed PAR together with A alloantigens of (A×CBA)F₁ spleen cells and (b) budding receptors bound anti-receptor antibody. CBA B lymphocytes did not interfere with these reactions. A search for putative T suppressor cells in the F₁cell population was unsuccessful. PAR formation and anti-RS antibody consumption by reappearing receptors differed temporally: receptors forming PAR were present after a delay lasting 8 h; receptor structures fixed anti-RS antibody as early as 5 h after being cultivated. With due caution, these results might reflect processes operating in maintenance of transplantation tolerance, suggesting that this condition is a serum-mediated suppression of long duration. The suppression would encompass continued neutralisation of receptors for the alloantigen to be tolerated by anti-T-cell receptor antibody formed by the F₁ chimeric cells within an animal with acquired transplantation tolerance.

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“…To determine alloantigen recognition by 'cell-bound' T-cell receptors, suspensions of parental cells from spleens or thymi were prepared in HBSS containing antibiotics (General Bio chemical Laboratories. Chagrin Falls, Ohio) as described [4,7]. To obtain cell-free T-cell receptors.…”

Section: Methodsmentioning

confidence: 99%

“…When it was originally described, the product of antigenic recognition (PAR) was shown to be a sensitive indicator of the amazingly fast recogni tion of alloantigen by receptors present on T lymphocytes [3][4][5]16], It was later demonstrated that alloantigenic recognition was not limited to viable T cells but that receptors shed from these cells were equally capable of recognizing alloantigens with yet higher speed [7,9,10], PAR formed in both of these interactions signified recognition by bona fide T-cell re ceptors of alloantigen. However, a third recognition system could also be revealed by the PAR assay: posttransplantation sera were found to con tain a principle capable of recognizing alloantigens in a manner similar to that of T-cell receptors.…”

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confidence: 99%

Studies on the Product of Antigenic Recognition I.

Ramseier¹,

Lindenmann²

1977

Pathobiology

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A product of antigenic recognition (PAR) was produced whenever receptors for alloantigens from T lymphocytes or a principle present in T-cell dependent alloantisera interacted with alloantigen. With two forms of the PAR assay (direct and indirect) the mechanisms underlying these interactions have been analyzed. For the interaction of T-lymphocyte receptors with alloantigen measured with direct PAR assays, the following conclusion emerged: upon confrontation with alloantigen, receptors (if not already present in secreted form) had first to be released from T-cell membranes. Shed T-cell receptors interacted with alloantigens by solubilizing them. Both processes could be prevented by fixing cells with formaldehyde. Release of T-cell receptors was temperature-dependent, solubilization of alloantigens was not. Because in mixed cell cultures receptors had first to be shed, this process was considerably slower and, in concordance with temperature dependence of receptor release, took place only at 37 °C. Titration of T lymphocytes with ‘bound’ receptors by the direct PAR test revealed that in the presence of excess alloantigen 10² T cells sufficed to give measurable responses. Supernates of parental strain lymphocytes containing numerous T-cell receptor specificities could be depleted of one of them. Alloantisera raised in presence of T helper cells (‘T alloantisera’) contained a principle capable of recognizing alloantigens, alloantisera incited in the absence of T helpers (‘B alloantisera’) did not. The recognizing principle appeared to be IgG. Like T-cell receptors, it was capable of solubilizing alloantigens form target cell membranes. B alloantisera lacked this capacity and their alloantigen-recognizing moiety was found to be monomeric IgM. The mode of interaction of this IgM with alloantigen most likely consisted in fixation to and shielding of antigen.

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Quantitative studies on antigenic recognition. II. Kinetics of the recognition event

Cited by 16 publications

References 20 publications

Cellular Receptors

Cellular Receptors

Transplantation Tolerance at the T-Lymphocyte Receptor Level II.

Studies on the Product of Antigenic Recognition I.

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