The T cell receptor: its repertoire and role in thymocyte development.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
P Marrack
Publications and source records attributed to P Marrack.
Superovulation and recovery of zygotes from Nubian and Alpine dairy goats.
Thirty-five purebred dairy goats (18 Alpines and 17 Nubians) were subjected to a superovulating hormone program consisting of an 11-d 6alpha-methyl-17alpha-acetoxy-progesterone; (MAP; 60 mg) intravaginal sponge treatment; 125 ug i.m. injections of the prostaglandin F(2alpha) analogue cloprostenol on d 1 and 9 of vaginal sponge treatment; and a 3-d, twice-a-day injection of 2.5 mg of pituitary follicle stimulating hormone (FSH-P) i.m. starting at day 9. Vaginal sponges were pulled the morning of day 11 at the time of the fifth FSH-P injection. Of 40 initiated superovulatory cycles, 33 does (10 Alpines and 23 Nubians) responded with an average of 17.7 (range 1 to 29) ovulations. There was no significant difference between the breeds with respect to corpora lutea (CLs) plus follicles ovarian response. A significantly greater (P< 0.05) number of Nubian does were in estrus and mated by 36 h after MAP sponge removal. All does that responded to treatment had done so within 72 h of sponge removal. Of the seven (17.5%) does that showed no estrous response to hormone treatment, six were Alpines (P < 0.01). Six goats (two Alpines and four Nubians) were subjected to a second hormone treatment cycle after a 45-d rest. Five of six does responded to a second hormone treatment cycle with four of five responding with a lower total ovarian response. The interval from sponge removal to mating did not affect the stage or quality of eggs harvested. Rather, the interval from mating to surgical flushing determined the stage of egg development. All animals examined from 24 to 32 h after initial mating had not ovulated. By 50 h, 20 of 22 does had ovulated. A total of 242 ovulated eggs (63%) was harvested, of which 199 (82%) were fertilized. Day 7 flushings yielded 36 eggs (67%), of which 28 (78%) were fertilized. This rate of superovulation, fertilization, and embryo recovery lends credibility to this technique in its ultimate objective of rapidly increasing the number of offspring from superior animals.
Journal Article↗
T cell receptor/MHC interactions in the thymus and the shaping of the T cell repertoire.
Explore the source record for details and available documents.
Animals↗
The T cell repertoire may be biased in favor of MHC recognition.
The receptors of two T cell hybridomas that recognize class I and class II major histocompatibility complex (MHC) molecules, respectively, have been compared. In both cases these receptors are hybrid molecules formed as a result of cellular fusion. The receptors contain the same alpha chain, contributed by the tumor cell fusion partner, and related beta chains, contributed by the normal T cell component. Thus, surprisingly, the same alpha chain can contribute to recognition of class I and class II MHC molecules. Moreover, the finding that in two independent examples hybrid receptor molecules created randomly by in vitro cell fusion recognize MHC supports the theory that the T cell repertoire has an intrinsic affinity for MHC.
Antibodies, Monoclonal↗
Synchronized rearrangement of T-cell gamma and beta chain genes in fetal thymocyte development.
Kinetics of mouse T-cell gamma gene rearrangements in ontogeny were determined as an approach to understanding the possible role of these genes in the development of fetal thymocytes. Two of these genes (C gamma 1 and C gamma 2) rearranged rapidly during days 14 to 17 of the gestational period in BALB/c mice. Moreover, these rearrangements seemed to be tightly synchronized with rearrangements of T-cell receptor beta chain genes in the same cells. It is suggested that the early transcriptional activity of gamma genes, which precedes that of beta chain genes, may not reflect the functional activation of these genes. Nevertheless, productive and therefore potentially functional gamma gene rearrangements precede surface expression of T-cell receptors in the thymus by 2 to 3 days, which is compatible with a role for gamma gene products in thymocyte development prior to antigen-specific stages.
Age Factors↗
The major histocompatibility complex-restricted antigen receptor on T cells. IX. Role of accessory molecules in recognition of antigen plus isolated IA.
Antibody inhibition studies were done to determine which molecules on the surface of the T cell hybridomas other than their receptors for antigen plus IAd were involved in interaction with antigen-presenting B cells, with artificial IAd membranes on glass beads, or with anti-receptor antibodies coupled to Sepharose beads. We found that T cell LFA-1 was only involved when B cells were used to present antigen plus IAd, whereas T cell L3T4 was involved in the response of T cells to antigen plus IAd either on cells or in artificial membranes, but not if anti-receptor antibodies were used to stimulate the T cells. From these results we concluded that LFA-1 may be involved in the recognition of a ligand on cells that was not present in artificial membranes, but that L3T4 might interact with a nonpolymorphic portion of class II molecules present in both intact antigen-presenting cells and the antigen-presenting artificial membranes.
Animals↗
The role of LFA-1 in class II restricted, antigen-specific T-cell responses.
We have studied the role of the murine lymphocyte function associated antigen-1 (LFA-1) in the major histocompatibility complex (MHC)-restricted responses of a panel of T-cell hybridomas to protein antigens. Monoclonal antibodies to LFA-1 showed a differential blocking effect in these responses that correlated with the overall "sensitivity" of a given hybrid to antigen and MHC as defined by other criteria already reported. This result differs completely from similar experiments in the CTL system where all clones regardless of their overall "avidity" for target cells are very sensitive to the blocking effects of anti-LFA-1. Further, we show that no blocking effects are observed in the response of our hybridomas when Class I or Class II transfected fibroblasts or cultured 3T3 fibroblasts are used as synthetic antigen presenting cells and the result is unaltered by preincubation of such cells with interferon-gamma (IFN-gamma).
Animals↗
The antigen-specific, major histocompatibility complex-restricted receptor on T cells.
Explore the source record for details and available documents.
Alleles↗
The role of the T-cell receptor in thymocyte maturation: effects in vivo of anti-receptor antibody.
The T-cell receptor, which recognizes antigen plus a product of the major histocompatibility complex, has been postulated to drive T-cell maturation in the thymus by engaging major histocompatibility complex proteins expressed on thymic stromal cells. We tested this idea by injecting neonatal animals with an anti-receptor antibody, KJ16, that binds to about 20% of T cells and is capable of blocking receptor function. In the presence of this antibody, mature T cells bearing the KJ16 epitope failed to develop. On the other hand, although the antibody could be shown to bind to receptors on cortical thymocytes, it did not prevent the rapid expansion or survival of the bulk of the KJ16+ cells in this population. These results are consistent with the hypothesis that most cortical thymocytes arise by a receptor-independent mechanism and that only a small proportion of these cells mature by a process dependent on receptor-major histocompatibility complex interactions.
Animals↗
H-2-linked Ir gene control of VH determinant(s)-specific helper T cells.
The fact that helper T cells (Th) recognize antigen in the context of class II MHC antigens is well documented. T cells specific for immunoglobulin (Ig) determinants have been demonstrated as have Th cells that interact with B cells in an idiotype (Id)-restricted manner. It is still controversial whether or not such T cells recognize idiotype in an MHC-restricted fashion. In tackling this problem it is important to have a T cell population selected by the introduction of the Ig bearing the determinant(s) in question and to have both the T cell and B cell populations unbiased by prior intentional exposure to specific exogenous antigen. Thus, the likelihood of such specific antigen-induced interactions is reduced and a clearer view of the Ig-induced interaction can be obtained. With this in mind, we found that T cells from B10.D2 mice immunized with normal BALB/c serum Ig were able to stimulate the response of BALB/c B cells to sheep red blood cells (SRBC) in vitro. H-2-linked Ir gene control was revealed by the ability of these Th cells to recognize BALB/c Ig in association with H-2d (BALB/c) but not H-2b (BALB.B). Through the use of Igh congenic mice, BAB/14 and C.B20, we found the Th cells to be specific for VH (idiotypic) rather than CH (allotypic) determinants; the determinant(s) in question was apparently expressed on some BALB/c anti-SRBC antibodies since these Th cells could help anti-SRBC responses but not anti-horse or anti-burro RBC responses. This conclusion of idiotypic specificity was supported by the fact that these Th cells could be primed with either IgM or IgG from BALB/c serum, one BALB/c anti-SRBC hybridoma protein but not two others or a BALB/c IgM myeloma protein, and by the fact that absorption of the serum on SRBC prior to separation of the Ig for immunization removed the priming ability of that Ig preparation. From the use of B cell mixing experiments, it was determined that the restriction elements of H-2 complex and the appropriate Ig determinants had to be borne on the responding B cells, suggesting that direct T-B collaboration was involved in the Th cell action. Therefore, by priming with normal serum Ig we have generated Th cells which act through direct interaction with responding B cells via a VH determinant(s). In addition, unlike the findings of others using different methods of priming Id-specific Th cells, these Th cells are under H-2-linked Ir gene control.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
T cell receptors in the thymus.
Explore the source record for details and available documents.
Animals↗
Genetic markers of the antigen-specific T cell receptor locus.
The restriction enzyme Eco RI reveals DNA cleavage sites that serve to distinguish the gene locus believed to encode the beta subunit of the major histocompatibility complex (MHC)-restricted, antigen-specific receptor of the T cell in BALB/c mice from that of SJL/J mice. A monoclonal antibody, KJ16-133, also distinguishes BALB/c and SJL/J, because it recognizes an allotypic marker present on a cell-surface heterodimer believed to function as the MHC-restricted, antigen-specific T cell receptor. This study has shown that these two markers cosegregate in a set of BALB/c X SJL/J recombinant inbred (RI) mouse strains, permitting the conclusion that they are linked to within 3 centimorgans of each other, and to the kappa locus on chromosome 6. The tight linkage between these independently derived, totally different T cell markers substantially strengthens the argument that they characterize the MHC-restricted antigen-specific receptor of the effector T cell.
Alleles↗
Major histocompatibility complex-restricted antigen receptor on T cells. VIII. Role of the LFA-1 molecule.
We show that the LFA-1 molecule on T cells does not play a role in the stimulation of T cell hybridomas by certain targets, namely antigen presented by L cell derivatives or polyvalent anti-receptor antibody. These results suggest that LFA-1 may act by binding to ligands that are not present on all cells. We hope this result will help us and others to establish the true role of LFA-1 in T cell responses.
Animals↗
T cell receptors for responses to Mls determinants and allo-H-2 determinants appear to be encoded on different chromosomes.
Previous studies have shown that T cell clones specific for strong Mlsa,d determinants concomitantly display apparently random reactivity to allo-H-2 determinants. One explanation for this finding is that T cell recognition of Mlsa,d and allo-H-2 determinants is controlled by separate sets of receptors. If these receptors were chromosomally unlinked, karyotypically unstable T cell hybrids with dual reactivity for Mlsa,d and particular allo-H-2 determinants would be expected, occasionally, to lose reactivity for one set of determinants, but not the other. The results presented here provide direct support for this prediction.
Animals↗
Effect of prostaglandin E2 on the gamma-interferon induction of antigen-presenting ability in P388D1 cells and on IL-2 production by T-cell hybridomas.
The effect of prostaglandin E2 on the gamma-interferon (IFN-gamma)-mediated induction of Ia expression and antigen-presenting activity in macrophage cell lines was studied. Using a lymphokine preparation obtained from the T-cell hybridoma FS7-20.6.18 (known to produce interferon) to induce the expression of Ia in P388D1 cells, the influence of PGE2 on this phenomenon was studied. Screening of the cell cultures by indirect immunofluorescence using an anti-I-Ad monoclonal antibody confirmed the inhibitory effect of PGE2 in the induction of I-Ad. However, the inhibition of the antigen-presenting ability of these cells, as measured by their capacity to stimulate interleukin 2 (IL-2) production by antigen-specific, I-region-restricted (Ag/I) T-cell hybridomas, was more difficult to demonstrate and was only evident when using low concentrations of Ia-inducing lymphokines or when using "low avidity" T-cell hybridomas. The latter were distinguished by the limited response (in the form of IL-2 production) that was observed when they were tested with P388D1 cells that had been induced with IFN-gamma. By contrast, PGE2 had profound inhibitory effects on the ability of T-cell hybridomas to secrete IL-2 in response to Ag/I or concanavalin A. These results suggest that although PGE2 inhibits the full induction of Ia on macrophages, it has little effect on the induction of Ag/I presentation by the same cells, probably because most T cells require relatively low levels of Ia on the surface of presenting cells. T-cell responses to Ag/I are inhibited, however, because of the effects of PGE2 on the T cells themselves.
Animals↗
Expression of antigen-specific, major histocompatibility complex-restricted receptors by cortical and medullary thymocytes in situ.
We have examined the distribution of the antigen-specific, major histocompatibility complex-restricted receptor on mouse thymocytes in situ, using immunohistochemical techniques and the monoclonal antibody KJ16-133. This antibody reacts with the beta chain of the receptors on about 20% of peripheral murine T cells. Of the cortical thymocytes reacting with KJ16-133, cells with only cytoplasmic staining were most frequently observed. Such cytoplasmic staining was not observed in the medulla. Occasional cortical cells had low levels of surface expression, which was almost invariably patched in the region of contact with epithelial cell processes. KJ16-133+ medullary thymocytes had high levels of uniform surface labeling. These results suggest that thymic selection of MHC restriction and/or tolerance may occur in the cortex, where the receptors on maturing thymocytes interact with MHC proteins on epithelial cells.
Animals↗
The T cell receptor: the alpha and beta chains define idiotype, and antigen and MHC specificity.
Three independent T cell hybridomas were isolated that have identical specificities for antigen and products of the major histocompatibility complex (MHC). All three react with the same clone-specific antireceptor antibody, and Southern blots show all three contain the same rearranged alpha and beta genes. Variants of one of these hybridomas, DO-11.10, were isolated that had lost the ability to respond to antigen plus MHC. These proved to have lost the DO-11.10-specific alpha or beta genes or both. Fusion of alpha-loss variants to beta-loss variants restored reactivity. These results indicate that the specific recognition of antigen plus MHC is determined solely by the alpha/beta-containing T cell receptor.
Animals↗