Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A murine B-cell lymphoma bearing the class II major histocompatibility complex molecule I-Ak was cultured with the protein antigen hen egg white lysozyme (HEL). The I-Ak molecules were purified, and their associated peptides were extracted for characterization. Five HEL peptides were identified. Four contained the 10 amino acid residues HEL 52-61 (DYGILQINSR) but were heterogeneous in length and flanking residues. This core sequence is known to confer a high binding affinity for I-Ak. One additional peptide contained the amino acid residues HEL 48-60. These data demonstrate that the HEL epitope containing residues 52-61 is the most abundant HEL epitope presented on the major histocompatibility complex of the antigen-presenting cells and consequently explains its immunodominance.
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PMID:Identification of the naturally processed form of hen egg white lysozyme bound to the murine major histocompatibility complex class II molecule I-Ak. 132 33

M protein from type 5 group A streptococci has been identified as a member of the family of polyclonal T cell activators termed superantigens because it preferentially stimulates T cells bearing specific V beta elements of the T cell receptor (TCR). In this study the molecular and cellular requirements for presentation of this protein to T cells were investigated. Only accessory cells (AC) expressing class II major histocompatibility complex (MHC) molecules were capable of supporting T cell activation in response to a 22 kDa fragment of M protein (pep M). Despite the need for class II elements, processing of pep M5 by the antigen-presenting cells (APC) was not required for T cell proliferation induced by pep M5. Fixation of APC by paraformaldehyde (PF) treatment impaired their ability to induce optimal T cell proliferation in response to pep M5 without significantly affecting interleukin (IL-2) production. In contrast, PF-fixation of cells from the B cell lymphoma line, Raji, did not affect their ability to present pep M5 to human T cells. Addition of rIL-1 and IL-6 to PF-treated APC restored pep M5-induced blastogenesis. Our data suggest that pep M5 directly associates with HLA class II molecules forming a complex that can induce IL-2 production but not optimal proliferation by T cells. Additional signals provided by the AC are required to trigger optimal T cell proliferation in response to this superantigen.
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PMID:Metabolically active antigen presenting cells are required for human T cell proliferation in response to the superantigen streptococcal M protein. 157 92

Methylation patterns in the major histocompatibility complex (MHC) class II Eb locus have been analyzed in cell lines representative of different cell types; in particular those with phenotypes found at various stages of B cell development. A series of variant B cell lymphoma lines which serves as a model in which to investigate mechanisms regulating class II gene expression in normal peripheral B cells has been examined. Eb methylation patterns have also been determined in various healthy mouse tissues. The pattern of methylation of the Eb locus varies between different cell lines and tissue types such that hypomethylation is associated with gene expression. There appears to be a methylation pattern which is permissive for class II gene expression and which is characteristic of a variety of cell lines, but is lost in cell lines representing terminally differentiated class II nonexpressing plasma cells. Another methylation pattern has been identified which is found in cloned cell lines selected for expression of very high levels of cell surface class II product. The patterns of methylation associated with MHC class II expression involve changes in methylation sites located within the first intron and several kilobase pairs 5' of the promoter, but no changes were observed in the 3' end of the locus. Moreover, the different methylation patterns do not map to the prominent CpG rich cluster located 5' of the Eb promoter and which remains completely methylated regardless of transcriptional status.
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PMID:Hypomethylation of MHC class II Eb gene is associated with expression. 163 42

Treatment of splenic B lymphocytes and certain B-lineage cell lines with the mitogen lipopolysaccharide (LPS) and the lymphokine interleukin-4 (IL-4) induces expression of germ line immunoglobulin C epsilon transcripts and class switching to the C epsilon gene. We show that LPS-plus-IL-4 induction of germ line epsilon transcripts (termed I epsilon transcripts) occurs at the transcriptional level in an Abelson murine leukemia virus-transformed pre-B-cell line. A 1.1-kb region of DNA surrounding the I epsilon promoter endows inducible transcription to a heterologous reporter gene stably transfected into these cells; such inducible expression depends on combined treatment with LPS and IL-4. Analyses of constructs transiently introduced into a B-cell lymphoma line demonstrated that LPS-plus-IL-4-inducible expression can be conferred by a 179-bp segment of DNA spanning the I epsilon transcriptional initiation site. Mutational analyses demonstrated that this expression depended on DNA sequences within a conserved region directly upstream from the I epsilon transcriptional initiation region. One nuclear protein that is constitutively expressed in normal B cells binds to the downstream end of the conserved sequence; its binding specificity correlates with the functional effect of several mutations. Two additional proteins, which are induced by IL-4 treatment of splenic B cells, bind to the transcription initiation sites of I epsilon. These proteins are indistinguishable in binding assays from proteins previously shown to bind an enhancer region of the class II major histocompatibility complex gene A alpha.
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PMID:Identification of a conserved lipopolysaccharide-plus-interleukin-4-responsive element located at the promoter of germ line epsilon transcripts. 192 63

Microvascular endothelial cells (EnC) in primary B cell lymphoma of the gastrointestinal tract were immunohistochemically studied. Based on the morphological structure, the microvasculatures were divided into high endothelial cell vessels (HEV) and flat endothelial cell vessels (FEV). There were distinct phenotypic differences between HEV and FEV in lymphoma tissues. HEV were characterized as OKM1- OKM5-, accompanied by the cluster of non-neoplastic T lymphocytes, and FEV were OKM1- OKM5+ not accompanied by T lymphocyte infiltration. Factor VIII-related antigen was clearly identified in both EnC, and major histocompatibility complex (MHC) class II antigens and interleukin 1 were absent or only faintly visible on EnC in lymphoma tissues, whereas they were expressed on EnC in non-lymphoma tissues. These findings suggest that microvascular EnC in primary B cell lymphoma of the gastrointestinal tract lack a property as antigen-presenting cells, and that HEV are involved in the migration of non-neoplastic T lymphocytes.
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PMID:Immunohistochemical characterization of microvascular endothelial cells in primary B cell lymphoma of the gastrointestinal tract. 199 11

The staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) has potent stimulatory effects on murine and human lymphocytes. This is the consequence of TSST-1 binding to major histocompatibility complex (MHC) class II molecules and the engagement in a V beta-restricted fashion of the T cell receptor by the TSST-1-MHC class II complex. Using radioligand and functional assays we have recently shown that TSST-1 binds to all HLA-DR (n = 14), HLA-DQ (n = 2) and HLA-DP (n = 2) phenotypes tested. In this study, we have examined the ability of murine MHC class II molecules to bind TSST-1. Specific high-affinity binding of TSST-1 was detectable to unfractionated BALB-c (H-2d) and C57BL/6 (H-2b), but not to C3H (H-2k) spleen cells. The Kd of this binding estimated from Scatchard analysis was in the same nanomolar range as the Kd of binding of TSST-1 to HLA-DR. Binding of 125I-labeled TSST-1 to BALB/c-derived B cell lymphoma lines and to L cell transfectants correlated with the expression of I-A molecules, but not with the expression of I-E molecules. Furthermore, I-A+, I-E- cells but not I-A-, I-E+ cells were able to support TSST-1-induced T cell proliferation. The binding affinity of TSST-1 for I-Ak appears to be much lower than for I-Ad. L cell transfectants expressing hybrid DR alpha: I-E beta k molecules, but not those expressing I-E alpha k: DR1 beta molecules, could bind TSST-1 and efficiently support TSST-1-induced T cell proliferation. This suggests that minor differences in the highly homologous I-E alpha and DR alpha chains are critical in determining the affinity of the MHC class II molecule for TSST-1. These results demonstrate that the binding of TSST-1 to MHC class II molecules in the mouse, in contrast to humans, is strongly influenced by phenotype. Analysis of the molecular basis of these differences may help to localize staphylococcal exotoxin binding sites on MHC class II molecules.
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PMID:Binding of toxic shock syndrome toxin-1 to murine major histocompatibility complex class II molecules. 220 97

Cell-mediated immunity against cancer cells primarily involves class I major histocompatibility complex (MHC)-restricted cytotoxic T cells and natural killer (NK) cells. To investigate whether T4+ cytotoxic T cells also have a role in tumor-specific immunity, mice were immunized with a B cell lymphoma. T cell hybridomas were constructed from the immune spleen cells and analyzed for their cytotoxic ability against the immunizing lymphoma. A T4+, Lyt-1+ hybridoma cell line was developed (103L2) which specifically killed the immunizing tumor cells but not normal B cells or a range of other tumor cells of B or non-B origin. This cytotoxic hybridoma cell line differed from Lyt-2+ cytotoxic T lymphocyte cells and NK cells, commonly identified with cytotoxicity, in a number of important ways. First, the cells were class II MHC restricted; second, interleukin-2 was released from activated effector cells; and finally but most importantly, innocent nonparticipating bystander cells were also killed. The significance of this observation was that normal cells were protected, although a broad range of tumor cell types, including tumor antigen-negative mutants, were killed. It is therefore conceivable that T4+ cytotoxic T cells might play an important role in tumor immunity through the direct recognition and lysis of tumor cells while any tumor variants, arising due to antigen loss, would remain susceptible through the bystander killing effect and normal cells would remain unaffected. These results strongly suggest that tumor-reactive T4+ cytotoxic T cells belong to a new category of effector cells with an important role in tumor-specific immunity.
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PMID:Evidence for an involvement of T4+ cytotoxic T cells in tumor immunity. 246 95

Mouse class II major histocompatibility complex genes have been shown to be regulated at the level of transcription for both tissue-specific and inducible expression. In particular, IFN-gamma induction of the class II genes has been shown to occur at the transcriptional level, although the role that additional post-transcriptional mechanisms of regulation may play in this induction is not known. To evaluate IFN-gamma effects on transcriptional and post-transcriptional events of class II gene expression, we examined the rate of decline of class II transcription, steady-state mRNA, and cell surface protein following the removal of IFN-gamma from maximally stimulated WEHI-3 cells (an IFN-gamma inducible, myelomonocytic cell line). We determined that transcription of class II genes almost completely returned to baseline levels eight hours after removal of IFN-gamma. However, the steady-state level of class II mRNA's required 4 days, and membrane Ia expression required 5 days to return to baseline levels. This decay was linear and allowed us to determine a half-life value of 16-20 h for class II transcripts. These data demonstrate that, following removal of IFN-gamma from fully stimulated cells, transcription of the class II genes declined rapidly, but mRNA was quite long-lived. We also assessed the class II mRNA stability in unstimulated WEHI-3 cells and the B-cell lymphoma. A20/2J, by actinomycin D treatment and northern blot analysis. In agreement with the IFN-gamma washout experiments, transcripts from all four class II genes were quite long-lived in these cell types, with a half-life greater than ten hours. These data support the concept that IFN-gamma acts primarily at the level of class II transcription and argues against IFN-gamma playing a major role in post-transcriptional modulation of class II expression.
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PMID:Evidence that IFN-gamma does not affect MHC class II gene expression at the post-transcriptional level in a mouse macrophage cell line. 250 46

A functional analysis of mutant class II molecules was conducted to identify regions important for antigen-specific T cell activation. Site-directed mutagenesis was used to construct a panel of mutant A beta k genes containing either single or multiple d allele substitutions in the beta 1 domain. The product of each of these genes was expressed with either the A alpha d or A alpha k polypeptide in the Ia-negative B cell lymphoma M12.C3. These mutant class II molecule-bearing cells were tested for their ability to present antigen to a panel of Ak-restricted T cell clones specific for various epitopes of myoglobin. Results from this analysis demonstrate that T helper clones recognized complex determinants interacting with multiple residues on the beta 1 domain and also requiring the haplotype-matched alpha 1 domain. This is in contrast to monoclonal antibodies that recognize a domain-specific, immunodominant region involving residues 40, 63, and 65-67. Every T helper clone was found to interact with a distinct pattern of residues, even among clones recognizing the same combination of peptide and major histocompatibility complex (MHC) molecule. The 3 for 1 residue substitution between k and d alleles at residues 65-67 was one of the most important, because it resulted in loss of ability to present antigen to 7 of 7 I-Ak-restricted T cell clones. These residues have been shown previously to comprise the immunodominant allo-specific serological determinants and to stimulate some alloreactive T cell clones. Substitution at residues 12 and 13 also abrogated antigen presentation to all the T cell clones, but this may be a consequence of a conformational change due to altered alpha beta chain pairing. Substitution at position 9, which is predicted to be located in the floor of the peptide-binding groove where it should not interact directly with the T cell receptor, enhanced presentation of the antigenic site 102-118 to some T cells and diminished it to others. This finding suggests a most interesting conclusion that the same antigenic site may bind in different conformations or orientations to the same MHC molecule, although an indirect effect on the conformation of the MHC molecule itself cannot be excluded. Substitutions at residues 85, 86 and 88 also abrogated the response of one T cell clone but not others specific for the same peptide with the same Ia molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antigen presentation to specific T cells by Ia molecules selectively altered by site-directed mutagenesis. 251 56

The stimulation of T cells by staphylococcal enterotoxins (SE) is strictly dependent on major histocompatibility complex (MHC) class II-bearing cells. The interaction between SE and MHC class II molecules was studied on the human B cell lymphoma Raji and its MHC class II-negative variant RJ 2.2.5. Affinity purification with SEA and SEB matrix allowed the isolation of HLA-DR-like molecules from detergent lysates of 125I surface-labeled Raji cells, but not from RJ 2.2.5 cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis also revealed preferences in the binding of other SE such as SED, SEE and toxic shock syndrome toxin 1 to DR-like molecules, SEC2 to HLA-DQ-like molecules and SEC3 to DR- and DQ-like molecules. Preadsorption of the different MHC class II MHC isotypes confirmed the preferential binding of SEA to DR and of SEC2 to DQ. The implications of these findings for the understanding of SE-induced T cell activation and the potency of SE as a tool in the study of MHC class II antigens are discussed.
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PMID:Different staphylococcal enterotoxins bind preferentially to distinct major histocompatibility complex class II isotypes. 259 4


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