Physical mapping, linkage analysis of a putative schizophrenia locus on chromosome 5q.

Two recent studies have suggested that a schizophrenia susceptibility locus may lie on the proximal long arm of chromosome 5. Partial trisomy of a 20-30 centimorgan region of chromosome 5 (5q11.2-13.

T cell interactions generated by synthetic peptides covalently linked to a carrier.

We have attempted to extend the synthetic peptide-carrier bridge concept of T cell-B cell interaction to T cell-T cell interaction. DNA synthesis of human CD4 cells that were sensitized in vivo to a native streptococcal antigen (SA) was stimulated in vitro with synthetic peptides (SP) derived from the sequence of native SA. The SP were linked to tetanus toxoid (TT) as a carrier which was recognized by primed T cells.

Phenotypic expression of Vicia villosa binding T cell subsets, as markers of contrasuppressor cells in systemic lupus erythematosus.

The hypothesis that autoimmune diseases might be due to a defect in immunoregulation was tested in systemic lupus erythematosus (SLE). We have applied the double immunofluorescence, flow cytometry technique to peripheral blood lymphocytes from patients with SLE. T cells were studied for their binding of the lectin Vicia villosa (VV) which is a phenotypic marker for contra-suppressor cells both in mice and humans.

Separation and characterization of a 14,000-dalton cyanogen bromide-generated peptide from a 185,000-dalton streptococcal antigen.

The cell surface streptococcal antigen (SA) (185,000 molecular weight [185K SA]) was isolated from Streptococcus mutans and digested with cyanogen bromide. Three major products with molecular weights of 100,000, 50,000, and 14,000 appeared within 1 h of digestion. Time course studies of digestion by polyacrylamide gel electrophoresis showed maximal intensity of the 14K band after 8 h.

CD4 and CD8 cell responses to herpes simplex virus in Behçet's disease.

The finding of part of the Herpes simplex virus type 1 (HSV1) genome in peripheral blood leucocytes of some patients with Behcet's disease (BD) led to investigations of T cell responses to HSV1 in this disease. A significantly impaired uptake of 3H-thymidine by CD4 cells was found in BD, as compared with healthy HSV1 sero-positive subjects. The impaired cellular response appeared to be specific to HSV1, as neither cytomegalovirus nor varicella-zoster virus showed depressed CD4 cell responses in BD.

The effect of immunization with a 14-kDa streptococcal antigen on primate T cell and B cell responses.

A streptococcal antigen (SA) of 185 kDa was isolated from Streptococcus mutans and this antigen induced in vitro helper, suppressor and contrasuppressor activities with primate peripheral blood lymphocytes. The 185-kDa SA was then treated by sodium dodecyl sulfate and yielded a 4-kDa SA which was capable of eliciting only helper activity. We have now cleaved the 185-kDa SA with cyanogen bromide, in an attempt to identify suppressor and contrasuppressor determinants.

A comparative investigation of three methods of separation of CD4 and CD8 cells from human peripheral blood cells.

A comparison was made of the phenotypic purities and functional efficiencies of CD4 and CD8 cell subsets, separated by three methods. CD4 and CD8 monoclonal antibodies were used for positive and negative selection of T cells by (a) panning, (b) red cell rosetting, and (c) complement mediated killing techniques. The viability of the CD4 and CD8 cell subsets, separated by any of the three methods and assessed by the dye exclusion method, was greater than 95%.

Characterization of human T8+ suppressor and contrasuppressor cells, separated by the lectin Vicia villosa.

The helper function of human T4+ cells acting on autologous B cells, in the presence of monocyte-enriched cells (MEC), has been studied using the hapten-carrier conjugate DNP-streptococcal antigen (DNP-SA). The antibody response can be suppressed by T8+ cells, but selection of a Vicia villosa lectin-non-adherent (T8VV-) subset enhances the suppressor function. The T8 Vicia villosa lectin-adherent (T8VV+) cells are not suppressive, rather they inhibit the T8VV- cell suppressor function.

C9 and factor B as acute phase proteins and their diagnostic and prognostic value in disease.

Some components of complement, such as C3, C9 and factor B, behave as acute phase reactants and their serum levels increase significantly in the course of inflammation. The diagnostic and prognostic significance of estimating the serum levels of C9 and factor B was evaluated in patients with Behçet's syndrome, recurrent oral ulceration and Crohn's disease, and the results were compared with those of measuring other acute phase reactants, such as C-reactive protein or alpha 1-antitrypsin. Longitudinal studies in these patients show a clear correlation between clinical indexes of the disease and levels of C9 and factor B.

An antigen-specific T8+ human clone of cells with a nonspecific augmenting function on the T4 cell-B cell helper interaction.

We isolated a T8+ T3+ Ia+ clone of cells from the peripheral blood mononuclear cells of a healthy subject. The clone was expanded and maintained with autologous feeder cells, interleukin 2, and a streptococcal antigen. The T8+ clone of cells responded specifically to the streptococcal antigen, in the absence of accessory cells, and released a soluble factor.

Use of monoclonal antibodies in local passive immunization to prevent colonization of human teeth by Streptococcus mutans.

Local passive immunization with monoclonal antibodies (MAbs) raised against streptococcal antigen (SA) I/II protects monkeys against colonization of teeth by Streptococcus mutans and the subsequent development of dental caries. In this study we extended the preclinical experiments to human subjects. In the first study of eight healthy subjects, four had anti-SA I/II MAb (immunoglobulin G2a [IgG2a]) and four had saline applied to their teeth on three occasions.

Recognition of carbohydrate and protein epitopes by monoclonal antibodies to a cell wall antigen from Streptococcus mutans.

The nature of the determinants recognized by a panel of monoclonal antibodies (MAbs) raised against a cell wall antigen of Streptococcus mutans (SA I/II) was investigated. Mild periodate oxidation of SA I/II showed that MAbs Guy 1, 2, 3, and 5 recognized carbohydrate epitopes on the antigen. Glycosidases were used to identify the nature of the sugars involved in their binding.

Free radical formation in crystals of guanine hydrochloride dihydrate: an ESR and ENDOR study.

Radiation-induced free radical formation in single crystals of guanine hydrochloride dihydrate has been studied at temperatures between 20 and 300 K using ESR and ENDOR spectroscopy. At low temperatures three radical species are trapped. Two of these are the C8 H-addition radical R1 previously analysed by Alexander and Gordy (1967) and the O6-protonated anion radical R2.

Antigen presentation by a subset of T8+ Ia+ cells to T4+ helper cells.

The helper function of human T4+ cells acting on autologous peripheral blood B cells was elicited by the hapten-carrier conjugate DNP-streptococcal antigen (DNP-SA), in the presence of monocyte-enriched cells. The antigen presenting function of monocyte-enriched cells can be replaced by a subset of autologous T8+ Vicia villosa lectin adherent (T8VV+) cells. Cell depletion studies confirmed that the T8VV+ cell presentation was mediated by a T cell since killing with anti-T3 antibody and complement removed the antigen presenting capacity of T8VV+ cells but not of monocyte-enriched cells.

Antibodies to a streptococcal antigen in gingival capillary and crevicular fluid washings, collected from man and non-human primates.

The local gingival antibody response was examined in actively-immunized rhesus monkeys and in human natural immunization to the cell-surface streptococcal antigen (SA I/II). A technique was developed to collect gingival capillary and crevicular fluid washings (GCCFW) from monkeys and human subjects with clinically normal gingiva. The thin crevicular epithelium and the adjacent capillary plexus are pierced with a probe and the resulting mixture of capillary blood, tissue fluid and crevicular fluid are collected by repeated washing of the gingival crevice.

Local active gingival immunization by a 3,800-molecular-weight streptococcal antigen in protection against dental caries.

Local gingival immunization was attempted in an effort to confine the immune response to the oral cavity and bypass the systemic immune response. A low-molecular-weight (3.8K) streptococcal antigen (SA) I/II was applied 10 times over a period of 1 year to the gingival crevices of rhesus monkeys.

Comparative study of antigen binding T cells separated by Vicia villosa or streptococcal antigen and the effect of HLA class II antigens.

The antigen binding capacity and function of T cells which adhere to the lectin Vicia villosa (VV) or to streptococcal antigen (SA) have been studied. VV-adherent T8+ cells (T8+ VV+) bind 125I-SA whereas VV non-adherent T8+ cells (T8+ VV-) bind little SA. Similarly, SA-adherent T8+ cells (T8+ SA+) bind 125I-SA specifically, whereas SA-non-adherent T8+ cells (T8+ SA-) show little binding of 125I-SA.

Local passive immunization by monoclonal antibodies against streptococcal antigen I/II in the prevention of dental caries.

Local passive immunization with monoclonal antibodies (Mc Ab) to Streptococcus mutans was attempted as an alternative approach to active systemic immunization. We prepared an immunoglobulin G class Mc Ab to the cell surface protein determinant of streptococcal antigen I/II and applied it repeatedly to the teeth of rhesus monkeys. This resulted in decreased colonization by S.

The helper and suppressor functions of primate T cells elicited by a 185K streptococcal antigen, as compared with the helper function elicited by a 4K streptococcal antigen.

Helper and suppressor functions of human T lymphocytes that act on antibody-forming B cells were elicited by a large 185K streptococcal cell wall antigen. However, a small 4K streptococcal peptide elicited helper but no suppressor function. These differences in the functional activities of the large and small m.

The role of a human antigen specific T8+ cell subset in antigen presentation, helper function and contrasuppression.

Regulation of the human immune response was studied by sequential separation of subsets of T cells, followed by assessment of their helper and suppressor functions in a series of reconstitution experiments. T8+ lymphocytes were separated by panning on streptococcal antigen (SA) coated plates into T8+ SA-adherent cells (T8+SA+) and T8+ SA-non-adherent cells (T8+SA-). The helper and suppressor functions of the T8+SA+ and T8+SA- cells, reconstituted with T4+ helper cells were then studied by a direct antibody forming cell assay.