Upon conjugation with cognate antigen-presenting cells (APCs), T lymphocytes undergo a sustained [Ca(2+)](i) increase resulting from the engagement of TCR and of accessory molecules with ligands expressed on the surface of APCs. We investigated the contribution of the accessory molecule CD2 to the activation of phospholipase Cgamma1 (PLCgamma1)/calcium pathway in antigen-stimulated T cells. We show that CD2 binding with its ligand CD58 expressed on the surface of APCs augments and sustains antigen-induced [Ca(2+)](i) increase in individual T cells interacting with APCs. We also show that in conditions in which CD2-CD58 interaction is impeded, the recruitment of PLCgamma1 to the immunological synapse (IS) is reduced. Interestingly, in these conditions PLCgamma1 phosphorylation in the regulatory tyrosine 783 is also defective. Our results indicate that TCR- and CD2-derived signals converge for the recruitment and activation of PLCgamma1 at the IS and shed new light on the accessory function of CD2 in T cell activation by specific antigen.

The phenomenon of idiotypy or individual antigenic specificity is one of the most fascinating in immunology (1-3). Clearly, this phenomenon appears to be intimately linked to the two major problems of the immune system: the origin of antibody diversity and the regulation of the immune system (4).It has frequently been assumed that idiotypy could be explained by the somatic mutation theory. Different idiotypes were considered to be different somatic variants, appearing from very similar germ-line genes. However results from our laboratory (the Laboratory of Animal Physiology, Universit6 Libre de Bruxelles, Rhode-SaintGen~se, Belgium) and from the Pasteur Institute, Paris (4-11) indicate that, in fact, the total idiotypic repertoire is more or less the same in all rabbits and mice, with exceptions that have been discussed elsewhere (7). Briefly, these conclusions stem from experiments in which it was possible to elicit the synthesis of a specific idiotype in a randomly chosen animal. The rationale behind the experiment was suggested by network concepts (4,(12)(13)(14). If we suppose that rabbit X, which does not express idiotypes from rabbit 1, nevertheless contains silent lymphocyte clones precommitted to the synthesis of idiotypes from rabbit 1, it should be possible to relieve these silent clones from suppression by raising immunity against suppressor cells. In principle, specific suppressors should bear autoanti-idiotypic receptors. Therefore, conventional anti-idiotypic antibodies to anti-peptidoglycan antibody (Abl) 1 (denoted Ab2) were raised, purifed, and injected into other rabbits for the synthesis of anti.anti-idiotypic antibodies (Ab3). Rabbits who were making Ab3 were then injected with the original antigen. Using several antigenic systems, the data show that: (a) After injection of antigen, nearly all the rabbits synthesized antibodies that were idiotypically crossreactive with the starting Abl (denoted Abl'). (b) Although the bulk of Ab3 did not recognize antigen, Ab3 and Ab 1' shared some idiotypic specificities because anti-antianti-idiotypic antibodies (Ab4) also recognized Abl and Abl' antibodies. (c) Ab4 behaved like Ab2 and diversity did not seem to increase along the chain of immunization.These data suggest clearly that suppression is dominant in the immune response.* Supported by grants from the Belgian Government. t Recipient of a doctoral fellowship from I. R. C. I. A. Z Abbreviations used in this paper: Abl, anti-peptidoglycan antibody(ies); Abl', antibody(ies) that were cross-reactive with the starting Abl; Ab2, anti-idiotypic antibody(ies) to Abl; Ab3, anti-anti-idiotypic antibody(ies); Ab4, anti-anti-anti-idiotypic antibody(ies); Abl-F1, Abl produced by the offspring; BSA, bovine serum albumin; PBS, phosphate-buffered saline. 1024 j. ExP. MED.

In this paper, we have considered the problem of selection of available repertoires. With Ab2 as immunogens, we have used the idiotypic cascade to explore potential repertoires. Our results suggest that potential idiotypic repertoires are more or less the same within a species or between different species. A given idiotype "à la Oudin" can become a recurrent one within the same outbred species or within different species. Similarly, an intrastrain crossreactive idiotype can be induced in other strains, even though there is a genetic disparity between these strains. The structural basis of this phenomenon has been explored. We next examined results showing the loss and gain of recurrent idiotypes without any intentional idiotypic manipulation. A recurrent idiotype can be lost in a syngeneic transfer and a private one can become recurrent by changing the genetic background. The change of available idiotypic repertoires at the B cell level has profound influences on the idiotypic repertoires of suppressor T cells. All these results imply that idiotypic games are played by the immune system itself, a strong suggestion that the immune system is a functional idiotypic network.

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