T cells cooperating in the induction of delayed-type hypersensitivity act via the linked recognition of antigenic determinants.

Abstract

A requirement for specific cellular collaboration has been demonstrated for the induction of humoral antibody (1-3), cytotoxic T cells (4,5), and for those helper T cells able to help the induction of B cells (6). Leung and Ada (7) have recently shown that antigen-specific cells can significantly enhance the primary in vitro induction of delayed-type hypersensitivity (DTH)a to influenza virus. We independently developed an in vitro system in which the induction of significant DTH reactivity is dependent on the presence of antigen-specific helper T cells. We used this system to determine the antigen recognition requirements by which these helper T cells act in the induction of DTH precursor cells.A phenomenon referred to as carrier specificity in the elicitation of DTH has been reported in the literature (8, 9), i.e., animals sensitized to a hapten on a given carrier will respond with DTH reactivity only when challenged with the hapten on the same carrier as was used for sensitization. This phenomenon has been insufficiently characterized to ascertain whether it is simply quantitative, in that only a small amount of the DTH reactivity is directed against the hapten, or whether it reflects either a requirement for specific cellular collaboration in the elicitation of DTH and/or that the DTH effector cells are specific for neoantigenic determinants created by coupling the hapten to the carrier. In any case, the phenomenon does not bear on the cellular requirements for inducing DTH and is in this sense different from the classical carrier effects described for the induction of humoral responses.The mechanism by which antigen-specific cells cooperate in the induction of B and helper T cells is known to be most effective when the two specific classes of cells recognize determinants that are physically linked to one another (10,11). With the recent establishment of experimental systems that allow DTH to be induced in vitro (12, 13), it has become possible to determine the cellular requirements for the induction of DTH. The experiments described in this paper were designed to test whether (a) specific cellular collaboration was required for the induction of DTH and * Supported by a grant from the Medical Research Council of Canada to the MRC group on immunoregulation, and a studentship and research allowance from the Alberta Heritage Foundation for Medical Research awarded to M. J. Tucker.1 Abbreviations used in this paper: BRBC, burro erythrocytes; CRBC, chicken erythrocytes; DTH, delayedtype hypersensitivity; FCS, fetal calf serum; FGG, fowl gamma globulin; FGG-BRBC, fowl gamma globulin physically coupled to burro erythrocytes; FGG-MRBC, fowl gamma globulin physically coupled to mouse erythrocytes; i.v., intravenous; MRBC, mouse erythrocytes; RBC, erytbrocytes; s.c., subcutaneous; Thy-1, thymus-derived cell marker.J. Exo. MED.

The Cooperation between Two CD4 T Cells Induces Tumor Protective Immunity in MUC.1 Transgenic Mice

“…The second is that this was accomplished by enlisting the response of tumor (self)-specific CD4 T cells through the help provided by CD4 T cells specific for a nonself-determinant. This mechanism is consistent with predictions based on associative recognition of linked T cell determinants (29) and validates the basic tenet of the two-signal model for T cell activation (9,30). We had previously demonstrated that the simultaneous injection of plasmids coding for -VTSA-and -NVDP-in different sites of the same organ did not generate immunity to MUC.1 (8), ruling out that -NVDP-may serve merely as adjuvant.…”

Th-1 polarization is regulated by dendritic-cell comparison of MHC class I and class II antigens

“…Through the use of peptide antigens and other experimental systems, investigators have previously demonstrated that priming of an active CD8 ϩ T-cell response in vivo requires covalent linkage between the MHC class II epitope that binds the CD4 ϩ T-cell receptor (TCR) and the MHC class I epitope that attracts the cognate CD8 ϩ effector cell; the implication being that such epitopes must be present in the same APC for the induction of a productive immune response. [46][47][48][49] Clearly, however, other mechanisms governing specificity must regulate CD8 responses, otherwise almost any soluble antigen might provide help for CD8 ϩ T cells recognizing almost any presented MHC class I peptide. Our observations detail a mechanism by which such specificity might be imparted.…”

Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections

“…We start from the premise, for which we believe there is much indirect and direct evidence, that the activation of CD4+ pTh cells in general requires CD4+/CD4+ T cell interactions mediated by the recognition of linked antigenic epitopes. These interactions between specific T cells are envisaged to be mediated by the recognition of antigens presented by antigen presenting cells (APCs), such as B cells or macrophages, by the interacting CD4+ T cells [35,36]. A valid description of the decision criterion must account for the conditions of immunisation known to determine whether Th1 or Th2 cells are generated.…”