Mls determinants recognized by T cells.

The relationship among different minor lymphocyte stimulatory locus (Mls) determinants, Mlsa, Mlsb, Mlsc and Mlsd, remains unclear. Because of the high degree of cross-reactivity between Mlsa and Mlsd determinants, the weak stimulatory capacity of Mlsc, and the generally non-stimulatory nature of Mlsb, some investigators have recently suggested that Mls is composed of only a single expressed allele originally defined as the a and d alleles. In order to clarify the nature of Mls determinants, T cell clones positively selected for reactivity to the three stimulatory Mls determinants, Mlsa, Mlsc and Mlsd, were generated and their specificities defined by extensive genetic studies.

Analysis of two distinct B cell activation pathways mediated by a monoclonal T helper cell. II. T helper cell secretion of interleukin 4 selectively inhibits antigen-specific B cell activation by cognate, but not noncognate, interactions with T cells.

A single monoclonal T helper (Th) clone can activate B cells in two distinct pathways; a cognate pathway requiring a major histocompatibility complex (MHC)-restricted T-B cell interaction, and a noncognate pathway not requiring an MHC-restricted T-B cell interaction. The present study was undertaken to investigate whether Th cells mediating a given immune response provide further regulatory function to B cells other than helper function. It was demonstrated that conditions of high antigen concentration which activate a noncognate B cell activation pathway simultaneously inhibit IgG responses.

Pattern of heart disease in Ethiopia as seen in a cardiology referral clinic.

385 patients were seen in the cardiology clinic of Tikur Anbessa Hospital, Addis Ababa, Ethiopia over 20 months. Of 338 with defined pathology, 152 had rheumatic heart disease, 47 were hypertensive, 39 had cardiomyopathy, 36 had congenital heart disease and 24 arrhythmia. Average age of rheumatics was 25.

Expression of T cell receptor V beta 8 determinants on antigen-specific T helper factor.

The ability of cell-free T helper cell products to provide helper activity in B cell antibody responses has been studied. The supernatants of activated T helper cells were sufficient to support hapten-specific IgG antibody responses by B cells in the absence of intact T cells. Moreover, this help was both antigen-specific and major histocompatibility complex (MHC)-restricted: T cell clone supernatant helped only when the hapten recognized by B cells was covalently linked to the carrier protein for which the corresponding T helper cell was specific; and this help was effective in supporting responses of only those B cells which express an MHC type corresponding to the MHC specificity of the cloned T cell.

The expression of Mlsc determinants on Mlsa, Mlsb, and Mlsx prototypic strains.

In the mouse system, specific determinants other than major histocompatibility complex (MHC) gene products are capable of inducing strong primary proliferative responses in naive T cells. These determinants are encoded by at least two gene loci designated as minor lymphocyte stimulatory (Mls) loci. In order to elucidate the biological role of the Mls system, an effort has been initiated to clarify the fundamental immunogenetic characteristics of the Mls system.

Structure and expression of class I MHC genes in the miniature swine.

The genome of the miniature swine, unlike other species, contains a relatively small class I MHC gene family, consisting of only seven members. This provides an excellent system in which to identify and characterize the regulatory mechanisms which operate to both coordinately and differentially regulate the expression of a multi-gene family. The structure of class I SLA genes, like other class I genes, consists of eight exons encoding a leader sequence, three extracytoplasmic domains, a transmembrane domain and intracytoplasmic domains.

Mls is not a single gene, allelic system. Different stimulatory Mls determinants are the products of at least two nonallelic, unlinked genes.

Mls determinants share with MHC products the unique property of stimulating T cells at extraordinarily high precursor frequencies. The Mls system was originally described as a single locus on chromosome 1, with four alleles, Mlsa, Mlsb, Mlsc, and Mlsd, that encode polymorphic cell surface structures. However, the fundamental issues of polymorphism and allelism in the Mls system remain controversial.

Cytotoxic T lymphocyte recognition of a xenogeneic major histocompatibility complex antigen expressed in transgenic mice.

Introduction of a porcine major histocompatability complex (MHC) class I gene (PD1) into the genome of a C57BL/10 (B10) mouse has been shown to lead to cell surface expression of the porcine MHC antigen, SLAPD1 in a transgenic mouse. The PD1 product expressed on spleen cells from the transgenic mice stimulated B10 spleen cells in a mixed lymphocyte culture to generate PD1-specific cytotoxic T lymphocytes (CTL). The CTL were PD1 specific since they lysed transgenic splenic blast cells and PD1-transfected L cells, but not B10 blasts or control L cells.

Secretory processes in lymphocyte function.

The secretion of immunoglobulin by plasma cells has been considered a classical example of the "non-regulated" pathway of protein secretion, in which newly synthesized protein is processed by the Golgi, packaged into small vesicles, and immediately secreted without intracellular storage. In the case of lymphokine secretion by T lymphocytes, it is generally not clear whether this non-regulated pathway is also being used, as opposed to the "regulated" pathway which has been proposed to operate in the cytotoxic lymphocyte mechanism. In this case, as in mast cells and endocrine cells, proteins are synthesized and then stored in cytoplasmic granules.

Clonal analysis of the Mls system. A reappraisal of polymorphism and allelism among Mlsa, Mlsc, and Mlsd.

Only two sets of antigenic determinants are recognized by T lymphocytes at uniquely high precursor frequencies: those encoded by the MHC and those encoded by Mls. The structural as well as functional characteristics of MHC products have been extensively analyzed. In contrast, little information concerning the nature of Mls genes or their products is available.

Different specificities of cloned T cells assessed by in vitro proliferation assays and by the ability to mediate skin graft rejection in vivo.

The experiments presented here have compared the specificities of T cell clones as determined by in vitro proliferative responses and their specificities as reflected by their ability to mediate skin graft rejection in vivo. Two proliferative T cell clones with distinct in vitro specificities were evaluated for their ability to mediate rejection of skin grafts from C57BL/10 Scn nu/nu mice. Clone 14.

Analysis of two distinct B cell activation pathways mediated by a monoclonal T helper cell. I. MHC-restricted activation of B cells by an IL 2-dependent pathway.

The present study was carried out to determine whether the MHC-restricted and MHC-unrestricted B cell activation pathways mediated by a single cloned Th cell are separable, and whether these two pathways are mediated by distinct mechanisms. It was demonstrated that the two B cell activating functions of a single cloned Th cell could be separated by their sensitivity to irradiation. It was shown that MHC-restricted B cell activation is mediated by a radiosensitive Th cell function, whereas MHC-unrestricted B cell activation is mediated by a radioresistant function of the same Th cell.

T cell recognition of Mls. T cell clones demonstrate polymorphism between Mlsa, Mlsc, and Mlsd.

The determinants encoded by the minor lymphocyte stimulating locus (Mls) are defined as determinants that induce strong T cell proliferative responses in primary mixed lymphocyte reactions. Although the Mls locus was originally described as having four alleles, a, b, c, and d, a number of recent observations have led several investigators to challenge the idea that Mls is truly a polymorphic system. To better define this system of determinants recognized at high frequency by T cells, the present studies were undertaken to evaluate the polymorphism of Mls products.

Ocular and stabilization feedback: an evaluation of two EMG biofeedback control procedures.

This study evaluated the adequacy of two novel EMG biofeedback control procedures. During a single training session, 36 subjects received either contingent EMG feedback from the frontal region (Veridical), contingent feedback for vertical eye movements (Ocular), or a feedback condition where the signal increased with deviations in any direction from baseline EMG levels (Stabilization). The results supported the use of Ocular but not Stabilization feedback as a control procedure in frontalis EMG biofeedback studies.

The T cell repertoire for recognition of a phylogenetically distant protein antigen. Peptide specificity and MHC restriction of staphylococcal nuclease-specific T cell clones.

Previous studies (1) have indicated that the repertoire of murine T cells specific for a potentially complex protein antigen is in fact specific for a limited number of antigenic epitopes on that antigen in association with a given Ia molecule. Since those studies generally analyzed responses to antigens that differ in only a few amino acids from homologous murine molecules, it was possible that tolerance to self proteins was responsible for the limited T cell repertoire seen in responses to closely related proteins. It was therefore of interest to determine whether T cell recognition of a structurally and phylogenetically more distant protein molecule would also show specificity for a limited number of immunodominant peptides on that molecule.

Cross-reactive recognition by antigen-specific, major histocompatibility complex-restricted T cells of a mitogen derived from Mycoplasma arthritidis is clonally expressed and I-E restricted.

In order to determine whether or not the major histocompatibility complex (MHC)-encoded restriction element used by a T cell in the recognition of its primary antigen affected its ability to be cross-reactively stimulated by MAS (a soluble product of Mycoplasma arthritidis), a panel of cloned, soluble antigen-specific I-A- and I-E-restricted T cells were tested for their ability to cross-reactively recognize and respond to MAS. Initial studies indicated that all of the cloned T cells tested were capable of responding to MAS in the presence of genetically E alpha E beta-expressing (I-E+), but not E alpha E beta-non-expressing (I-E-) accessory cells (AC). However, subsequent studies demonstrated that the ability of most of these T cell clones to mount proliferative responses to MAS in the presence of I-E+ AC was dependent upon the presence of Lyt-1+2- T cells in the irradiated spleen cells which were used as AC sources.

Expectancy effects on relaxation instructions: physiological and self-report indices.

Two sessions of relaxation instructions were administered under high and low expectancy conditions. Fifty-four college students scoring high on a self-report measure of anxiety served as subjects. Live and taped abbreviated progressive muscle relaxation instructions and a self-relaxation condition were equally effective in reducing within-session self-report and physiological indices of anxiety.

Cell-mediated immune responses to syngeneic tumors. I. Identification of two distinct CTL effector pathways which differ in antigen specificity, genetic regulation, and cell surface phenotype.

It has been demonstrated previously that draining lymph nodes (DLN) from tumor-immunized mice contain a population of lymphoid cells that are capable of differentiating into functional antitumor cytotoxic T lymphocytes (CTL) during in vitro culture. In the present studies, it was observed that DLN cells from either C57BL/10 (B10) or C3H mice that had been footpad-immunized with syngeneic tumor cells differentiated into CTL during a 4-day in vitro culture in the absence of added antigen. The specificity patterns of the CTL thus generated, however, were quite different in the two strains.

Antigen-induced T suppressor cells regulate the autoreactive T helper-B cell interaction.

The T suppressor (Ts) cell population that functions to regulate antigen-specific MHC-restricted T helper (Th)-B cell interactions also regulates the activation of B cells by cloned autoreactive Th cells. Activated Ts cells were generated by in vivo priming and restimulation in vitro with high concentrations of the specific priming antigen. Once generated, this Ts population inhibits the Th-dependent activation of primed B cells by both antigen-specific and autoreactive T cells in an antigen-nonspecific manner.

Influence of helper T cells on the expression of a murine intrastrain crossreactive idiotype.

The requirement for idiotype-specific helper T (Th) cells in the generation of a major intrastrain crossreactive idiotype was investigated. This idiotype, designated CRIA, is associated with a large proportion of anti-p-azobenzenearsonate (anti-Ar) antibodies in A/J mice. Secondary in vitro responses were studied.

T cell regulation of B cell activation. Lyt-1+,2-T cells modify the MHC-restricted function of heterogeneous and cloned T suppressor cells.

Previous studies have shown the existence of both heterogeneous Lyt-1-,2+ suppressor (Ts) cells and cloned Lyt-1+,2- Ts cells which, despite the difference in their Lyt phenotypes, functioned in a similar antigen-specific and major histocompatibility complex (MHC)-restricted fashion to suppress the antibody responses generated by cloned helper T (Th) cells and hapten-primed B cells. Our studies were carried out to assess in further detail the genetically restricted cell interactions that mediate this immune response suppression. We show that the activation of both heterogeneous and cloned Ts cells is antigen-specific and MHC-restricted under our experimental conditions.