Direct receptor:receptor interactions between T and B lymphocytes: idiotypic restriction in the antibody response to a cloned helper T cell receptor.

The concept of an immunological network includes the possibility of interactions between receptors on T and B lymphocytes, and such interactions, should they occur, might be expected to influence the repertoire of receptors in each set of cells. Indeed, B cell idiotype specific helper T cells, both MHC-restricted and MHC-unrestricted, have been reported and have been shown to influence the expression of the B cell repertoire. Likewise, it has been reported that B cells may influence the specificity of both regulatory and MHC-restricted T cells.

The role of the murine L3T4 molecule in T cell activation: differential effects of anti-L3T4 on activation by monoclonal anti-receptor antibodies.

MHC restricted T cells can be divided into two subsets based on the mutually exclusive expression of the cell surface differentiation antigens L3T4 and Lyt-2 in the mouse. Expression of the L3T4 marker is correlated most strictly with recognition of foreign antigen in association with self class II MHC molecules, or Ia molecules. Less stringently correlated with L3T4 expression is the recognition of unmodified self or non-self Ia molecules.

Transcripts of functionally rearranged gamma genes in primary T cells of adult immunocompetent mice.

The T-cell specific, rearranging gamma-chain genes bear striking resemblance to T-cell receptor and immunoglobulin genes, but the role of gamma remains unknown. A central problem is to understand the conditions under which gamma RNA is expressed in cells. The transcription of gamma is abundant in T cells of fetal thymi, but is negligible in peripheral T cells of adults, suggesting that gamma is involved in development of the T-cell repertoire.

Immune serum from mice contact-sensitized with picryl chloride contains an antigen-specific T cell factor that transfers immediate cutaneous reactivity.

This report describes an activity in serum from mice that were contact-sensitized with picryl chloride (PCl) 1 to 4 days earlier. Immune serum, when given i.v.

The specific direct interaction of helper T cells and antigen-presenting B cells.

Cell couples have been formed by mixing an antigen- and Ia-specific cloned helper T-cell line with a B-cell hybridoma presenting the antigen. By immunofluorescence observations, we have shown that the microtubule-organizing center (MTOC) inside the helper T cell, but not in the bound antigen-presenting cell, becomes oriented to face the area of specific cell-cell contact. This MTOC orientation is antigen- and Ia-specific, and thus provides direct evidence for the specific interaction of a helper T cell with a B cell.

Influence of immunoglobulin-dependent T cells on antibody class switching.

Normal and B cell-deficient, carrier-primed mice were irradiated and were adoptively transferred with B cells to evaluate the role of putative Ig- and B cell-dependent T cells in anti-hapten antibody responses. The response was analyzed by using the splenic focus assay, which allowed us to examine the frequency of responding B cells and the production of multiple isotypes by single precursor B cells. This analysis revealed that both primary and secondary B cells were activated at higher frequency in the spleens of normal recipients, and production of isotypes other than IgM and IgG1 was enhanced in normal recipients as compared with anti-mu-treated recipients.

Molecular characterization of antibodies bearing Id-460. I. The structure of two highly homologous VH genes used to produce idiotype positive immunoglobulins.

The heavy chain immunoglobulin genes encoding a variety of antibodies specific for DNP or Pasteurella pneumotropica and bearing the dominant idiotype of MOPC 460, Id-460, were cloned and sequenced. The VH genes encoding the M460 and D35 (DNP binding) antibodies were found to be homologous but not identical to the VH gene encoding the LB8 (P. pneumotropica binding) monoclonal antibody.

Autocrine growth inhibition of a cloned line of helper T cells.

The growth of T lymphocytes is dependent on the T-cell growth factor interleukin 2 (IL-2), which causes T cells bearing high-affinity receptors for IL-2 to proliferate. Most cloned helper-T-cell lines can be shown to both produce and respond to IL-2; thus, growth of such cells is by an autocrine mechanism. We report that the failure of the cloned murine T-cell line D10.

The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal.

The T cell surface molecules Lyt-2 and L3T4 are strongly correlated with the class of MHC gene product recognized by the T cell bearing them. The L3T4 molecule has been proposed to play a role in enhancing recognition of antigen:Ia by specific T cells. In the present experiments, we have explored the role of L3T4 in T cell activation by examining the effects of the L3T4-specific monoclonal antibody GK1.

Direct interactions between B and T lymphocytes bearing complementary receptors.

A murine cloned Th cell line specific for the antigen conalbumin in the context of self I-A molecules can be activated by low concentrations of soluble antireceptor mAb. By using an antireceptor mAb to shared antigenic determinants on T cell receptors, we have shown that the ability to be activated by soluble antireceptor mAb is an unusual, although not unique, feature of this cloned T cell line. This activation does not involve occult APC, FcR, or interaction between individual cloned T cells, as limiting-dilution analysis shows that individual cells of this clone will grow in the presence of the antireceptor antibody and IL-1 as stimulus.

Cell interactions in the immune system: the role of self recognition in the targeting of nonspecific effector molecules by helper T cells.

Helper T cells are activated by cross-linking of their receptors by antigen:Ia complexes on the surface of antigen-presenting cells and B cells. As a result of this cross-linking, the helper T cell releases several lymphokines that in turn affect the Ia-bearing cell with which the helper T cell is in contact. This interaction is cognate when the effect on the target cell is examined, but it operates by a mechanism that is neither antigen specific nor MHC restricted.

The immunobiology of T cell responses to Mls-locus-disparate stimulator cells. III. Helper and cytolytic functions of cloned, Mls-reactive T cell lines.

Mls-specific T cell clones derived by limiting dilution were tested for cytotoxic activity in a lectin-dependent 51Cr-release assay. All the T cell clones tested were cytotoxic in such an assay in apparent contrast to previous reports. However, only those target cells sensitive to cytolysis by other L3T4a+ cytolytic T cells were killed by Mls-specific T cell clones in short term 51Cr-release assays, possibly explaining this discrepancy.

Different phenotypic variants of the mouse B cell tumor A20/2J are selected by antigen- and mitogen-triggered cytotoxicity of L3T4-positive, I-A-restricted T cell clones.

The L3T4+, Lyt-2-, cloned BALB/c T cell lines 5.9.24 and 5.

Molecular characterization of antibodies bearing Id-460. II. Molecular basis for Id-460 expression.

Id-460+ immunoglobulins can be induced in vivo by immunization with dinitrophenyl (DNP) or P. pneumotropica and form two nonoverlapping groups of antibodies with respect to antigen binding specificity. In this study, using Id-460+ antibodies of differing antigen binding specificities, we compared on the molecular genetic level the five gene segment combinations (VH, DH, JH, VL, and JL) that encode the variable regions of these idiotype-positive immunoglobulins.

Modes of cell:cell communication in the immune system.

Different cell types in the immune system appear to mediate their effects by markedly different means. B lymphocytes couple information for specificity with information for function in a single long-range molecule, antibody. Major histocompatibility complex (MHC)-restricted T cells, which we have analyzed in detail, appear to recognize antigen only on the surface of cells bearing the appropriate MHC gene product.

The immunobiology of T cell responses to Mls-locus-disparate stimulator cells. II. Effects of Mls-locus-disparate stimulator cells on cloned, protein antigen-specific, Ia-restricted T cell lines.

Cloned, protein antigen-specific, Ia-restricted T cell lines frequently (approximately 20%) also respond strongly to stimulator cells from strains expressing stimulatory alleles at the chromosome 1-encoded Mls-locus. Furthermore, such responses are blocked by monoclonal antibodies specific for Ia antigens expressed by the stimulator rather than the responder cells. However, such responses show no specificity for polymorphic determinants on Ia molecules, although in such responses, as in primary and secondary T cell responses to stimulating Mls-locus alleles, I-E molecules appear to play a central role.

The immunobiology of the T cell response to Mls-locus-disparate stimulator cells. I. Unidirectionality, new strain combinations, and the role of Ia antigens.

The primary mixed lymphocyte reaction of T cells to Mls-locus-disparate stimulator cells differs from that to non-self Ia antigens in several respects. In the present experiments, the unidirectional nature of this response is shown in several strain combinations, including the newly detected Mlsa and Mlsa-like alleles expressed by strains PL/J, RF/J, and SM/J. All of these strains stimulate MHC-identical T cells strongly.