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At least 19 recordsLinked to original sources
PubMed1979

Adherent cell function in murine T-lymphocyte antigen recognition. IV. Enhancement of murine T-cell antigen recognition by human leukocytic pyrogen.

A macrophage-dependent, antigen-specific murine T-cell proliferation assay was utilized to examine the role of soluble products of murine and human adherent cells in the activation of T lymphocytes. Highly purified human leukocytic pyrogen, and supernates from both murine and human mononuclear phagocytes-macrophages stimulated the immune T-cell proliferative response to the multideterminant antigens dinitrophenyl-ovalbumin and keyhole limpet hemocyanin. The implications of these studies and the relationship of leukocytic pyrogen to human lymphocyte-activating factor are discussed.

Animals↗
PubMed1998

Class II MHC/peptide complexes on T cell antigen-presenting cells: agonistic antigen recognition inhibits subsequent antigen presentation.

Previous studies have shown that tolerogenic anti-CD4 (W3/25) and anti-LFA-1 mAb (LRTC1) which block T cell activation paradoxically enhance T cell-mediated antigen presentation. Lasting T cell APC (T-APC) activity requires and initial exposure of T cells to these mAb in the presence of professional APC and antigen. This study revealed a central mechanism regulating the duration of T-APC activity. T cell recognition of class II MHC complexes of T-APC catalyzed a rapid decay in the presentation of agonistic antigens, whereas partial agonistic signals decayed at a shower rate. Likewise, blockade of agonistic T-T cell autorecognition by these mAb led to the persistence of agonistic MHC/antigen on T-APC. The best predictor of T-APC activity was related to the ability of clonal T cells to respond to antigen presented by neighboring T cells. Strong responders were inefficient T-APC, whereas inefficient responders were strong T-APC. Addition of irradiated myelin basic protein (MBP0-specific responders to T-APC cultures specifically inhibited the subsequent presentation of MBP but not conalbumin, and vice versa. T-APC presentation of antigen to responder T cells also resulted in reduced surface expression of class II MHC I-A glycoproteins on T-APC. These findings indicate that agonistic recognition of antigen of T-APC specifically inhibits subsequent presentation of that antigen, whereas antagonistic MHC/antigen complexes are preserved for an enduring T-APC activity.

Animals↗
PubMed1992

Altered major histocompatibility complex-restricted antigen recognition by T cells from elderly humans.

Positive selection of T cells within the thymus gland leads to major histocompatibility complex (MHC)-restricted recognition of antigen by T lymphocytes. As the thymus gland involutes with age, altered MHC-restricted antigen recognition by T cells from elderly humans would be expected. We have tested this hypothesis by comparing the proliferative response of T cells and T cell clones from aged and young subjects to influenza determinants presented by autologous or allogeneic antigen-presenting cells (APC). Under conditions in which the allogeneic mixed lymphocyte reaction was minimal, T cells from six of seven aged donors but only one of seven young donors were stimulated by influenza vaccine presented by allogeneic APC. More importantly, one-half of the influenza-specific T cell clones derived from aged donors, but none of the clones derived from young donors, were activated by influenza vaccine presented by allogeneic APC. While 80% of the MHC-nonrestricted influenza-specific T cell clones expressed the gamma/delta T cell receptor, 20% of these clones expressed the alpha/beta T cell receptor. Thus, changes in MHC-restricted antigen recognition by T cells and in altered distribution of alpha/beta versus the gamma/delta T cell receptor bearing antigen-specific T cell clones occur with aging.

Adult↗
PubMed1984

The role of B cell surface Ia antigen recognition by T cells in B cell triggering. Analysis of the interaction of cloned helper T cells with normal B cells in differing states of activation and with B cells expressing the xid defect.

Two discrete mechanisms of T-B cell collaboration appear to exist. In cognate recognition, B cell triggering results from a direct recognition of antigen and MHC determinants at the B cell surface. Alternatively, B cells can be triggered by transstimulation, in which the Th cell is activated by an antigen-presenting cell to produce soluble factors which in turn trigger the B cell. This report addresses the question of whether antigen recognition at the B cell surface in association with Ia determinants delivers a signal to the B cell, which is qualitatively different from the signals delivered by the soluble mediators released by the activated Th cell. Previous reports from a number of laboratories suggest that cognate recognition is obligatory for the triggering of small resting B cells and B cells of the Lyb-5- phenotype, whereas enlarged B cell blasts and the Lyb-5+ subset can be triggered solely by soluble mediators. Contrary to these findings, the experiments described here indicate that B cells isolated in different states of activation from normal spleens on the basis of their buoyant density in Percoll density gradients, or unfractionated B cells from mice differing genetically due to the xid defect [Lyb-5- B cells from (CBA/N X BALB/c)F1 male mice], do not discriminate between the two modes of Th cell function. In both stimulation modes, the high density B cells, and the B cells from xid mice made very poor immunoglobulin secretory responses measured in terms of reverse plaque formation on protein A-coupled erythrocytes. When the responses of different density fractions of B cells were compared under conditions where stimulation occurred either directly or indirectly via transstimulation, the following hierarchy of responsiveness in both the proliferative and plaque-forming cell (PFC) responses was observed in the density fractions 60% greater than 65% greater than 70% greater than 75%. The hierarchy was the same in both modes of interaction and the deficiency of the high density, small B cells was far more marked in the PFC assay than in the proliferative assay. We conclude that the initial proliferative response of the resting B cell can be triggered comparably in vitro under conditions of direct or transstimulation. Thus, recognition of B cell surface Ia by Th cells is not obligatory for B cell activation and does not transfer an essential transmembrane signal to the B cell.

Animals↗
PubMed1986

I-A-restricted T cell antigen recognition. Analysis of the roles of A alpha and A beta using DNA-mediated gene transfer.

The contributions of A alpha and A beta chains, and of subregions of A beta, to Ia-restricted recognition of antigen by Th lymphocytes were analyzed using a panel of L cells transfected with various pairs of A alpha b,d, or k genes and recombinant or wild-type A beta b,d, or k genes. The A beta genes included all possible exchanges of the whole NH2-terminal (beta 1) domain or halves of the beta 1 domain among these three allelic A beta genes. The Ia+ L cells derived from such transfections were used as antigen-presenting cells with a 21 member panel of responding Ia-restricted T hybridoma cells of differing nominal antigen specificity and Ia-restriction. Special care was taken to account for quantitative variation in levels of Ia expression throughout the experiments. The results of this analysis reveal that (a) only 2 of the 21 Th cells recognized Ia molecules involving either a nonparental A alpha or a nonparental A beta chain, and in both cases the degeneracy extended to only one of the two other alleles tested. This suggests that allele specific contributions from both A alpha and A beta chains are important in restricted recognition for most, if not all I-A-restricted Th cells. (b) In no case did substitution of the A beta 2 domain from either of the alternative haplotypes lead to any functionally detectable effects, demonstrating that polymorphisms in the A beta 1 domain can entirely account for the restriction imposed on Th cell responses by the entire A beta chain. (c) For 90% of the cells tested, replacement of the NH2-terminal portion of the beta 1 domain with an allogeneic segment led to Ia molecules unable to elicit Th responses. Furthermore, of all the cells permissive of the substitution of one or other half of the beta 1 domain, only two permitted the substitution of sequence from both alternative haplotypes. Taken together, these data strongly suggest that antigen recognition by most, if not all, I-A-restricted Th cells involves contributions from both halves of the A beta 1 domain. These data suggest that the role of I-A molecules in restricted Th cell recognition of antigen depends on conformational determinants unique to a particular combination of polymorphic alpha and beta chains, and that multiple such sites exist on a single Ia molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Probing T cell antigen recognition: use of synthetic peptides.

The availability and use of synthetic peptides have significantly enhanced our understanding of T cell recognition of antigen. This review is an attempt to chronicle applications of synthetic peptide technology to examine various aspects of T cell recognition. Specifically, a historical prospective of T cell antigen recognition precedes a description of the use of synthetic peptides to probe T cell recognition in the context of a trimolecular complex, in terms of regulatory and cytotoxic T cells, with respect to T cell tolerance and the concept of immunodominance, and its relevance to autoimmunity.

Animals↗
PubMed1994

Comparison of age-dependent antigen recognition in two communities with high and low Trichuris trichiura transmission.

A previous ELISA-based study using whole worm extract, compared age-antibody profiles in two communities with high and low levels of Trichuris trichiura transmission (Needham et al., 1992). This showed that specific IgG1 levels mirrored infection intensity at the population level, while IgA levels exhibited a weak trend to remain elevated in the adult age classes in the area of highest transmission. This was interpreted as preliminary evidence for IgA-mediated resistance in the population with greatest prior experience of infection. The present study extends this work to compare IgG1 and IgA isotype recognition of separated antigens by Western blot between the two communities. Comparison of age-dependent antigen recognition in the two communities shows that both qualitative and quantitative recognition by IgG1 antibodies is related to the current intensity of infection (as assessed by eggs per gram of faeces, epg). The magnitude of the IgA response to separated antigens of 16-17 kDa and 90 kDa exhibits a stronger trend to remain elevated in adults and to reflect the past experience of infection: IgA antibodies are present at significantly higher levels in adults from the high transmission area compared with those from the community with low levels of T. trichiura endemicity, despite infection levels in these age groups being of similar magnitude. This comparative study therefore, provides further evidence to support a role for IgA in acquired immunity to T. trichiura in areas of intense transmission.

Adolescent↗
PubMed1987

Major histocompatibility complex (MHC) restricted antigen recognition: high frequency of human T-cell clones recognizing novel MHC class II determinants.

We have used antigen-specific human T-cell clones to study the relationship between MHC and antigen recognition specificities expressed by T cells. Tetanus toxoid (TT)-specific T-lymphocyte clones were derived from a immunized HLA-DR2,7 heterozygous donor by limiting dilution from peripheral blood mononuclear cells (PBM) restimulated with TT in vitro. Clones were screened for MHC-restricted antigen recognition against antigen-presenting cells (APC) from a panel of HLA-typed donors, using an in vitro T-cell proliferation assay. Several distinct patterns of antigen recognition were identified. In addition to T cells that recognized TT in association with donor class II MHC antigens, we found clones that simultaneously expressed self-restricted antigen recognition and alloreactivity, and clones with specificity for antigen in the context of MHC antigens not expressed by the T-cell donor. This was confirmed in inhibition studies using well-characterized monoclonal antibodies against class II MHC antigens to block specific proliferative responses. We propose a possible structure for the determinant recognized by two of the clones. These results suggest that the T-cell antigen receptor undergoes random or antigen-dependent changes in vitro, and that this may be a mechanism for somatic diversification of the T-cell repertoire.

Antibodies, Monoclonal↗
PubMed1998

[Antigen-recognition mechanism of T cells].

The antigen-recognition mechanism of T cells was reviewed from the standpoint of MHC-restriction. T cells recognize antigens presented by antigen-presenting cells in a MHC-restricted manner. CD4+ helper T cells recognize antigens with the context of MHC class II molecules, and CD8+ cytotoxic T cells recognize antigens with MHC class I molecules. The MHC class I molecule is composed of alpha-chain and beta 2-microglobulin, and MHC class II molecule is composed of alpha-chain and beta-chain. The T cell antigen receptor is composed of alpha-chain and beta-chain, or gamma-chain and delta-chain, and CD3 complex. Antigens are processed and presented by antigen-presenting cells to T cells in the context of MHC molecules. Furthermore, costimulatory factors such as adhesion molecules and cytokines are required for the full activation of T cells. The biological significance of the T cell antigen recognition mechanism is discussed from the standpoint of clinical application.

Antigen-Presenting Cells↗
PubMed1996

Human onchocerciasis in Nigeria: isotypic responses and antigen recognition in individuals with defined cutaneous pathology.

Antigen (Ag)-specific isotype responses to Onchocerca volvulus Ag (OvAg) were assessed by enzyme-linked immunosorbent assay and immunoblot in 123 residents of a mesoendemic area in northern Nigeria and 16 Nigerians from a nonendemic area. Individuals from an endemic area were divided into six groups on the basis of cutaneous onchocercal pathology: acute papular onchodermatitis (APOD), chronic papular onchodermatitis (CPOD), lichenified onchodermatitis (LOD), atrophy (ATR), depigmentation (DPM) and normal skin, high microfilarial load (NSHMF). Immunoglobulin (Ig)G1-4 levels were all significantly associated with residence in an endemic area after controlling for age and sex (all P values = 0.0001). Both IgG1 and IgG3 were significantly associated with onchocercal clinical category after controlling for age, sex, and microfilarial load (P = 0.0031 and 0.0035, respectively). The IgG1 and IgG3 responses were both highest in LOD and lowest in NSHMF and ATR, respectively. A significant inverse association was found between IgG1 levels and microfilarial load after controlling for age, sex, and clinical category (P = 0.0061). On immunoblotting, 20 (44.4%) of 45 individual onchocerciasis sera contained IgG4 antibodies against a band of 29-31 kD, which was not recognized by pooled sera from individuals with other filarial infections. There was heterogeneity of antigen recognition within each of the onchocercal clinical groups, which together with the small numbers examined by immunoblotting, limits interpretation. Nevertheless, some differences in patterns of antigen recognition were found between the onchocercal groups. The LOD group demonstrated prominent immunoreactivity in IgG1 and IgG3 while a general paucity of low molecular weight reactivity was seen with NSHMF in IgG1-3 subclasses, but there was no specific banding pattern that differentiated NSHMF from those with pathology. Comparison of microfilariae-positive (mf+) and mf- individuals with onchocercal skin disease revealed significantly higher levels of all IgG subclasses and higher overall scores on semiquantitative assessment of immunoblots for IgG1, IgG2, and IgG4 for mf+ individuals. Differing isotypic responses may play a role in the pathogenesis of the clinical spectrum of cutaneous onchocerciasis.

Adolescent↗
PubMed1977

Studies on the mechanism of lymphocyte-mediated cytolysis. IX. Relationships between antigen recognition and lytic expression in killer T cells.

The relationship between antigen recognition and lytic expression by killer T cells was studied by co-culturing two effector cell populations. When antigen recognition was bidirectional (e.g., b anti-d cells cultured with d anti-b) there was a loss of lytic activity in both populations. In contrast, when antigen recognition was unidirectional (e.g., a anti-d co-cultured with d anti-b) then the loss of lytic activity only occurred in that direction; i.e., there was a marked decline in the d anti-b activity but no change in the a anti-d population. These studies suggest: i) that mere proximity to a killer cell does not lead to target cell death; ii) that accommodation of the T cell's antigen receptor is necessary for the cell to express its lytic potential; and iii) there is direct linkage between the T cell's antigen receptor site and its killing mechanism.

Animals↗
PubMed1990

[Antigenic recognition of rats infected with Gnathostoma hispidum: comparison of antigens derived from the advanced third stage larvae of Gnathostoma hispidum and Gnathostoma doloresi].

To increase understanding of immune response of host against G. hispidum, antigenic recognition of rodent gnathostomiasis were identified by the immunoblot method after PAGE of the advanced third stage larvae of G. hispidum and G. doloresi. The molecular weight of the major antigenic bands of G. hispidum extracts were 35 kDa and 16 kDa, and of G. doloresi were 48 kDa, 37 kDa and 35 kDa. Of these bands, the 35 kDa antigen of G. hispidum and G. doloresi was recognized with the sera of rats infected with G. hispidum 5 weeks after inoculation. Lecting staining with endoglycosidase-H or hydrolytic degradation on nitrocellulose strips revealed that the 35 kDa band of G. hispidum possessed the mannose-rich oligosaccharides. On the other hand, the band of G. doloresi had the hybrid-type glycopeptides. The larval extracts and excretory-secretory materials of G. hispidum were not antigenitically identical.

Animals↗
PubMed1985

An induced fit hypothesis for antigen recognition by T lymphocytes: a role for specific antigen retention structures on antigen-presenting cells.

The nature of T lymphocyte recognition of foreign antigens is not known, despite recent advances in elucidating the cellular structures that may be involved in the specific interactions. The central difficulty in this process is that T cells respond to foreign antigen only in the context of major histocompatibility complex (MHC) antigens expressed by another antigen-presenting cell. In addition, T cells that interact with class II MHC antigens do not bind foreign protein antigens in their native form, but seem to recognize only proteolytic peptide fragments as the relevant antigen. The simplest explanation for these observations is that the class II MHC antigens themselves bind antigenic peptides to form the appropriate determinant that interacts with the antigen-specific T cell receptor. However, to date no such antigenic complex has been found with MHC antigens despite rigorous attempts at their demonstration. One alternative explanation described here is that there is no preexisting foreign antigen-MHC antigen complex prior to interaction with T cells, and it is the T cells that cause the two moieties to become associated for recognition by a single antigen-specific T cell receptor. Central to this mechanism is that foreign antigenic peptides must be associated with specific antigen retention structures (SARS) expressed by antigen-presenting cells which retain and protect the peptide on the cell surface. These SARS, upon interaction with T cell membrane moieties, would subsequently associate with MHC antigens. A hypothesis to describe this mechanism is developed to account for published observations of antigen processing by antigen-presenting cells and T cell antigen recognition, and makes several predictions that are experimentally testable. This mechanism is also generally applicable to other cellular interactions in which soluble peptide mediators may become associated with surface components of one cell type, and this newly formed complex is in turn recognized by a receptor on a second cell type to deliver functional signals.

Animals↗
PubMed1998

Imaging antigen recognition by naive CD4+ T cells: compulsory cytoskeletal alterations for the triggering of an intracellular calcium response.

Antigen recognition was analyzed at the single-cell level by using for the first time T cells which were not altered by in vitro selection, transfection or immortalization. The first consequence of antigen recognition by ex vivo naive CD4+ T cells from T cell receptor (TCR)-transgenic mice is the formation of a "contact zone" with the B cell presenting the antigen. The T cell intracellular calcium (Ca2+) response begins after a delay of 30 s on average, following the formation of the contact zone. The T cell response is entirely inhibited by either protein tyrosine kinase or actin polymerization inhibitors but, surprisingly, it is insensitive to inhibitors of phosphoinositide 3-kinase. Moreover, inhibition of microtubule polymerization and use of Ca2+-free medium do not prevent the beginning of the T cell response, but do reduce the stability of the contact zone and/or the amplitude of the Ca2+ plateau. The critical involvement of the cytoskeleton in antigen recognition on B cells introduces a checkpoint in T cell activation: the initial TCR engagement triggers a Ca2+ response only after an amplification step corresponding to a cytoskeleton-controlled increase in the number of engaged TCR.

Actins↗
PubMed1986

Hapten-specific cytotoxic T cell clones undergo somatic variation of their antigen recognition specificity.

Two experimental systems have demonstrated somatic variation of antigen recognition specificity of long-term cytotoxic T cell (CTL) clones. System 1 used CTL clone BT7.4.1 with strict specificity for Kb/TNP, which had been continuously cultured for 15 months in the presence of H-2b/TNP stimulator cells and interleukin 2. Upon removal of the TNP antigen from the cultures, 99% of the clone cells within about 10 cell divisions lost their ability to grow in the presence of antigen and interleukin 2 (lethal variants). Of the surviving 1%, about 60% retained the ability to lyse target cells in the presence of lectins but only 12% could be considered as "wild type" BT7.4.1 cells, i.e. they still specifically lysed H-2b/TNP-bearing target cells. The majority of the growing cells, thus, had to be considered as specificity loss variants. Several specificity loss variants were established in culture and were shown to express membrane-bound T cell "receptor" heterodimer similar to their TNP-specific ancestor, BT7.4.1. Principally the same types of variants were generated in cultures growing in the presence of TNP antigen, although in quantitatively reduced numbers. Under these conditions the specific stimulator cells appeared to impose a significant selective advantage for "wild type" CTL since even after 15 months the cultures fully retained their specificity for the nominal antigen. In system 2, the development of cytolytic fine specificity of a panel of 42 individual Kb/TNP-specific CTL clones was followed over a period of 8 months of in vitro culture. At the beginning of the test, 37 of these clones exhibited significant cross-reactivity for lysis of H-2k/TNP target cells. This number of cross-reactive clones continuously diminished with time and dropped to only 4 clones after 8 months in culture. All 42 clones retained their original Kb/TNP specificity and after losing their reactivity for H-2k/TNP usually showed no decrease but rather an increase in their cytotoxic activity towards Kb/TNP target cells. Loss of H-2k/TNP cross-reactivity was not accompanied by loss of Lyt-2 or of LFA-1 surface antigens or by loss of sensitivity of the cytotoxicity to inhibition by anti-Lyt-2 or by anti-LFA-1 antibody. We conclude from these observations that in vitro cultivated CTL clones, at least those of C57BL/6 anti-TNP-C57BL/6 specificity, are not stable in terms of their antigen recognition specificity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1976

Evidence for direct linkage between antigen recognition and lytic expression in effector T cells.

The relationship between antigen recognition and lytic expression by effector T cells was examined by coculturing two cytolytically active lymphoid cell populations. When antigen recognition between the populations could occur only in one direction, then cytotoxicity was expressed only in that direction and the population whose antigens were recognized lost its lytic activity. In contrast, the cocultured effector cell population fully maintained its lytic potential. This lack of reciprocal inactivation was taken as evidence that T-cell receptor accomodation by surface antigen is linked to the expression of cytolytic activity by effector T lymphocytes.

Animals↗
PubMed1997

Effects of epitope modification on T cell receptor-ligand binding and antigen recognition by seven H-2Kd-restricted cytotoxic T lymphocyte clones specific for a photoreactive peptide derivative.

We tested for antigen recognition and T cell receptor (TCR)-ligand binding 12 peptide derivative variants on seven H-2Kd-restricted cytotoxic T lymphocytes (CTL) clones specific for a bifunctional photoreactive derivative of the Plasmodium berghei circumsporozoite peptide 252-260 (SYIPSAEKI). The derivative contained iodo-4-azidosalicylic acid in place of PbCS S-252 and 4-azidobenzoic acid on PbCS K-259. Selective photoactivation of the N-terminal photoreactive group allowed crosslinking to Kd molecules and photoactivation of the orthogonal group to TCR. TCR photoaffinity labeling with covalent Kd-peptide derivative complexes allowed direct assessment of TCR-ligand binding on living CTL. In most cases (over 80%) cytotoxicity (chromium release) and TCR-ligand binding differed by less than fivefold. The exceptions included (a) partial TCR agonists (8 cases), for which antigen recognition was five-tenfold less efficient than TCR-ligand binding, (b) TCR antagonists (2 cases), which were not recognized and capable of inhibiting recognition of the wild-type conjugate, (c) heteroclitic agonists (2 cases), for which antigen recognition was more efficient than TCR-ligand binding, and (d) one partial TCR agonist, which activated only Fas (C1)95), but not perforin/granzyme-mediated cytotoxicity. There was no correlation between these divergences and the avidity of TCR-ligand binding, indicating that other factors than binding avidity determine the nature of the CTL response. An unexpected and novel finding was that CD8-dependent clones clearly incline more to TCR antagonism than CD8-independent ones. As there was no correlation between CD8 dependence and the avidity of TCR-ligand binding, the possibility is suggested that CD8 plays a critical role in aberrant CTL function.

Affinity Labels↗
PubMed1997

Antigen recognition characteristics and comparative performance in immunoaffinity purification of two monoclonal antibodies specific for the hepatitis B virus surface antigen.

In this paper we describe the antigen recognition characteristics, variable region base and amino acid sequence, and performance as immunoaffinity chromatography ligands of two MAb specific to the alpha determinant of the HBsAg, derived from the same fusion. We show that the epitope recognized by CB-Hep.0 (IgM) is probably associated to an intrachain disulfide bond in the antigen. On the other hand, CB-Hep.1 (IgG2b) recognizes a heat-resistant non-conformation dependent antigenic determinant on HBsAg. PCR-cloning and sequencing of the variable regions of these two MAb indicated that both heavy chain variable regions were originated from the usage of the same germinal V and J genes. However, the outstanding differences in the size of the VH CDR3, and the absolute difference in the light chain sequences, suggest that the hybridomas were originated from different precursor B lymphocytes. With respect to their use as immunoaffinity chromatography ligands for the purification of a recombinant HBsAg, we found that the IgM immunogel exhibited increased performance with respect to amount of eluted antigen, and final recovery. This difference in overall performance could be attributed to a series of factors: the higher valence number of IgM, a dissimilar distribution of IgM and IgG in the activated gel particles, and differences in antigen recognition between both MAb. Our results suggest that IgM antibodies may be useful in immunopurification, particularly if the antigen is structurally complex and has a high density of repeating epitopes.

Amino Acid Sequence↗