摘要:

AbstractT cell clones and subsequently hybridomas were generated from rabies virus‐immune C3H/He mice to an immunodominant epitope of the viral nucleoprotein, termed 31D, that had previously been identified by a 15‐amino acid‐long synthetic peptide. T cells to this epitope that by phenotypical and functional characteristics belonged to the T helper cell subset were shown to respond to most rabies and rabies‐related viruses. In order to define the minimal sequence needed to elicit a response from 31D‐specific T cell clones or hybridomas, a number of peptides of varied lengths,i.e.3–32 amino acids long, were tested. The ability of the peptides to induce a response was inversely correlated in their lengths,i.e., short peptides (3–5 amino acids long) had to be used at 106times higher concentrations as compared to long peptides (15 or 32 amino acids long). Conversely, the specificity of the T cell response was directly correlated to the length of the peptides,i.e., while the response to 15‐amino acid‐long peptides exhibited a high degree of specificity, the response to 3‐ to 5‐amino acid‐long peptides showed a high degree of flexibility. The long as well as the short peptides had to be presented in association with I‐Ek. We speculate that in this system the T cell receptor interacts predominantly with a peptide‐induced modif

ISSN:0014-2980    

DOI:10.1002/eji.1830210102

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe relative complement‐mediated lytic capability of the IgG subclass isotypes was studied using a matched set of mouse‐human chimeric anti‐(4‐hydroxy‐3‐nitrophenyl)acetyl (NP) antibodies. The subclass pattern was shown to be highly dependent on variations in antigen concentration and to lesser extent on variation in epitope patchiness, antibody binding affinity and complement concentration. In general, the IgG3 subclass was most effective in inducing cytolysis at the different conditions used and only at high antigen concentration did the IgG1 subclass mediated more efficient cytolysis than IgG3. The IgG2 isotype required a relative high antigen concentration to be cytolytic while the IgG4 isotype was not cytolytic at any of the conditions tested. These individual characters of each of the IgG subclasses makes it conceivable that a subtle system of immunoregulation exists among the

ISSN:0014-2980    

DOI:10.1002/eji.1830210103

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractAntigen‐specific murine CD4+T cell clones can be divided into functionally distinct subsets known as Th1 and Th2. To date these cells have been indistinguishable by surface phenotype. This report identifies two anti‐CD45R monoclonal antibodies (14.8 and C363.16A) that bind preferentially to Th2 cells. Further analysis of the CD45‐specific mRNA in Th1 and Th2 cells shows clear differences between these two cell types. Th1 cell clones express mRNA for the two smallest forms of CD45 containing none or only one of the alternatively splices exons. In contrast, Th2 cell clones express predominantly the high molecular weight isoforms of CD45 containing two or three of the alternatively spliced

ISSN:0014-2980    

DOI:10.1002/eji.1830210104

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractAntigenic stimulation with exogenous soluble proteins induces cytotoxic T lymphocytes (CTL) recognizing antigenic peptides presented on class II major histocompatibility complex (MHC) molecules. Such CTL have been shown to lyse preferentially B cells expressing immunoglobulin receptors reactive with the relevant antigens, presumably because such B cells can efficiently trap and present the antigen. Therefore, possible involvement of soluble protein antigen‐specific CTL in specific suppression of antibody responses has been hypothesised. In this report, keyhole limpet hemocyanin and ovalbumin‐specific, class II‐restricted CD4+CTL clones established from lymph nodes of immunized mice were examined for their suppressive activities on antibody production. When these CTL clones were added toin vitrosecondary cultures, genetically restricted, carrier‐specific suppression of anti‐2, 4, 6‐trinitrophenyl antibody production was observed. These data therefore demonstrate that CTL directed toward soluble antigens are capable of mediating specific suppression of antibody responses. Furthermore, the antibody response of MHC‐heterozygous F1lymphocytes was almost completely suppressed by a CTL clone restricted to one parental class II MHC antigen, indicating that the mechanism of suppression by these CTL is distinct from that by classical suppr

ISSN:0014-2980    

DOI:10.1002/eji.1830210105

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractHLA class II molecules are involved in the OKT3‐induced T cell activation, since monoclonal antibodies (mAb) to monomorphic determinants of class II antigens are able to inhibit T cell proliferation. This effect involves several of the events leading to T cell activation and proliferation,i.e.interleukin (IL) 1, IL 6 and IL 2 secretion and IL 2 receptor expression. The main target of the inhibition is represented by monocytes, and the interference of anti‐class II mAb in the direct interaction of monocytes with T cells is likely to play a relevant role in the inhibition mechanism. To test this hypothesis, we investigated in the present study the effect of anti‐class II mAb on the proliferation of T cells stimulated with mAb OKT3 in the presence of paraformaldehyde‐treated monocytes. We show that the inhibition of proliferation is specific and dose dependent, and seems to involve particular class II epitopes. Addition of fixed monocytes to inhibited T cell cultures restores proliferation to a moderate extent, only if monocytes are added within the first 12 h of culture, suggesting that class II antigens or spatially related molecules deliver signals concurrently with the mitogenic stimulus. The blocking capability of anti‐class II mAb was not restricted to the CD4+or the CD8+T cell subsets, suggesting that, under inhibitory conditions, these mAb affect other structures on the T cell surface, relevant to the monocyte‐T cell

ISSN:0014-2980    

DOI:10.1002/eji.1830210106

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe interaction of lymphocytes with the extracellular matrix plays an important role in the immune defence against tumor cells and virus‐infected cells. We have examined the effect of matrix proteins on the migration of large granular lymphocytes (LGL) through 3‐μm pores in Nuclepore filters in a Boyden invasion chamber. Fibronectin bound on the filter surface significantly increased (p<0.001) the capacity of LGL to migrate, whereas soluble fibronectin did not. In addition, a significantly higher (p<0.001) percentage of LGL was capable of migration through fibronectin‐coated filters than through untreated filters. With fibronectin‐coated filters, a strong enrichment of CD16+and CD56+CD3−cells with LGL morphology and reduction of CD3+cells was found among migrating cells when the incubation time was 4 h or less. Later agranular lymphocytes, mainly CD3+T lymphocytes, also started to migrate. Laminin coating of filters also facilitated migration, and when filters were coated with both fibronectin and laminin the increase in migration was equal to the sum of the increases induced by each protein alone. Interactions between cell surface and the Arg‐Gly‐Asp (RGD) peptide sequence of many matrix proteins had no role in the LGL migration through untreated flters. However, when filters were coated with either fibronectin or laminin, or with both, peptide containing the RGD sequence reduced migration to the level of untreated filter, whereas an Arg‐Gly‐Glu control peptide had no effect. Our results show that unstimulated LGL/natural killer cells are capable of rapid migration through matrix‐coated porous membranes, and that interactions between cell surface receptors and the RGD sequence of fibronectin and probably laminin are util

ISSN:0014-2980    

DOI:10.1002/eji.1830210107

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractMature T cells found in the lymph nodes and spleen have the capacity to become activated and to proliferate in response to foreign antigens. The response of the thymus to such immunization is less well understood. We have examined one aspect of the thymic response by determining the effect of peripheral immunization upon cell emigration from the thymus. BALB/c (Mls‐1b) mice were injected with spleen cells from DBA/2 (Mls‐13) mice, and Vβ6+(Mls‐13‐reactive) thymic emigrants were identified 3–30 days after immunization. Neither the rate of total cell migration from the thymus nor the proportion of Vβ6+cells was altered, even though the immunizing spleen cells elicited an immune response in the draining (parathymic) lymph nodes. The same immunogen caused deletion of Vβ6+cells in both the thymus and lymph nodes after intraperitoneal injection into the neonate. The inability of DBA/2 splenocytes to modify the development of adult thymocytes after intrathymic injection of the cells precluded the lack of entry into the thymus as the reason for the lack of any observed effect in the adult. Our results, therefore, indicate that the development of adult thymocytes is not modified by immunization, and suggest that the differing thymic response of mice injected as adults or neonates is related to changes in the intrathymic antigen presentation capacity associa

ISSN:0014-2980    

DOI:10.1002/eji.1830210108

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractImmunization of certain strains of mice with native type II collagen (CII) induces both development of arthritis and an antibody response to autologous CII. The autoantibody response in a high‐responder strain, the DBA/1 mouse, has been described earlier, and a number of monoclonal antibodies have been characterized for arthritogenicity and autoreactive binding to cartilagein vivoandin vitro. Here we map the antigenic epitope of one of these arthritogenic monoclonal antibodies (CII‐C1). It belongs to a group of antibodies recognizing the CNBr fragment α1(II)‐CB11 of CII. Using the enzyme‐linked immunosorbent assay technique, we show that the antibody reacts only with native, triplehelical CII, but not with other collagens. The antibody is able to stain specifically the CB11 fragment by immunoblotting, suggesting some partial renaturation of the CNBr fragment into triple‐helical structures after blotting. The binding site of CII‐C1 on CB11 was further focused by rotary shadowing of antibody‐labeled CII to a site 89 ± 8 nm from the amino end of CII, corresponding to the middle of CB11. This location was confirmed by cleavage of CB11 with trypsin, separation of the tryptic peptides by high‐performance liquid chromatography and dot‐blot analysis of the antigenic peptides with the CII‐C1 antibody. Sequencing of the single positive peptide located the antigenic epitope within the sequence GFAGQAGPAGAT‐GAPGRP (residues 316–333). Assuming 0.29 nm per residue, this corresponds to a position within 92–96.5 nm from NH2terminal end of CII. Apart from glycine residues, which are not exposed on the triple‐helical structure, only two amino acid residues (F‐x‐y‐Q) are conserved in CII from different species but are not found in the triple‐helix of other collagens except type IV collagen. Therefore, this structure is likely to be of critical importance for the binding of the CII‐C1 antibody. Of potential importance is that this structure is also found in certain other arthritogenic proteins such as 65‐

ISSN:0014-2980    

DOI:10.1002/eji.1830210109

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractAlthough many B lymphocytes contain two completely rearranged immunoglobulin (Ig) heavy (H) chain genes, only one of the alleles specifies a protein product. This phenomenon is termed allelic exclusion and is controlled in part by the membrane portion of Ig H chains. We have identified a mature B cell line derived from murine bone marrow that expresses two H chain proteins, γ3and γ2b. Proteins of appropriate size for the membrane and secreted forms of both H chains are produced and both IgG3and IgG2bare secreted from the cells. However, only IgG3is expressed on the membrane. Detailed restriction mapping of the H chain genes indicates that both are rearranged, one containing a VHJ558 gene linked to the γ3constant region and the other a VHS107 gene linked to the γ2bconstant region. Primer extension sequencing of the RNA reveals that the γ2bRNA is transcribed from the allele containing VHS107 sequences while the γ3RNA is transcribed from the allele containing VHJ558 sequences. Thus, this mature B cell line secretes two distinct antibody molecules but is allelically excluded at the level of surface Ig expression. This cell line provides a model system to study factors, in addition to aberrant rearrangement, that influence allelic excl

ISSN:0014-2980    

DOI:10.1002/eji.1830210110

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe novel mutant gene, lprcg, is allelic with lpr, but complements the gld gene in induction of lymphoproliferation. Mice with this autosomal recessive mutation, CBA/KlJms‐lprcg/lprcg(CBA‐lprcg), served in this study to analyze the abnormalities of bone marrow (BM) stem cells responsible for autoantibody production and lymphoproliferation by BM transfer experiments. Transferred CBA‐lprcgBM cells might have differentiated into so‐called double‐negative, anomalous lymphoid cells and caused production of autoantibodies such as anti‐DNA antibodies in the environment of normal CBA/KlJms−+/+ (CBA−+) mice. Macroscopic graft‐vs.‐host‐like disease as reported in lpr→non‐lpr BM transfer was not observed in these recipients. In this BM chimera, however, lymphoproliferation did not ensue and the host's lymph nodes became atrophic. The lymphoproliferation required the coexistence of lprcgBM cells and lprcglymph nodes in CBA−+ mice. The results indicate that the functions of the lprcggene are expressed at both BM and lymph node levels. Thus, this mutant strain of mice should provide an excellent model for analyzing aberrant lymphocyte differentiation from the BM cells leading to autoimmunity and l

ISSN:0014-2980    

DOI:10.1002/eji.1830210111

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY