Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MHC Class II (Ia) and invariant chain cooperate in the presentation of exogenous antigen by antigen presenting cells to T-helper cells. Both glycoproteins have been identified in the small intestine of the mature mouse. In this study, we examine the ontogeny of mRNA for three molecules; (Ii31, Ii41 and I-A beta) in whole intestine and in isolated epithelial cells. When RNA from whole intestine was analysed in northern blots using cDNA probe, Ii31 mRNA was present in Day 10 mice and at each 5 day time point thereafter; Ii41 and I-A beta were not detected by this technique. To examine ontogeny of Ii chain mRNA in enterocytes, RNA was purified from an enriched population of epithelial cells isolated after systemic perfusion with 30 mM EDTA in Day 21 and Day 28 and adult mice. Ii chain mRNA was not detected until Day 28 by blot hybridization. Reverse transcription of mRNA and amplification of the resultant cDNA by PCR revealed Ii41 and I-A beta as well as Ii31. RNA from Day 21 epithelial cells required five additional amplification cycles to attain cDNA levels equivalent to those found in Day 28 cells for Ii chain, and 10 additional cycles for I-A beta. In conclusion, Ii31, Ii41 and I-A beta mRNA increase rapidly in the enterocyte after weaning.
Mol Immunol 1992 Oct
PMID:Ontogeny of class II MHC mRNA in the mouse small intestinal epithelium. 132 14

The S49 cell lines are a unique series of tumor sublines isolated from a single BALB/c thymoma. Several different sublines were previously isolated from non-mutagenized cells using pharmacologic agents that would select for different stages of thymic development. In this report we show that all seven of the sublines studied express TL class I Ag confirming their derivation from immature thymocytes. This uniform TL expression is in contrast to the previously characterized locus-specific shut off of Kd,Dd, and/or LdAg by various S49 sublines. Furthermore, S49 sublines were found to display disparate CD4/CD8 expression. Whereas the unselected subline is a CD4+/CD8+ double positive, each of the selected sublines is singly positive for either CD4 or CD8. All seven sublines were found to be CD3+ and express alpha beta TCR heterodimers. To establish whether the S49 sublines have a monoclonal or polyclonal origin, their TCR rearrangements were compared. Based on the detection of identical but unusual TCR gamma rearrangements and similarity of the alpha and beta rearrangements, we propose that the S49 sublines probably had a monoclonal origin. However, significant differences between the TCR alpha and beta gene rearrangement were observed, suggesting that these sublines have undergone further differentiation at TCR loci in addition to CD4/CD8 and MHC loci. Evidence is presented that much of this phenotypic diversity preceded their in vitro selection.
Mol Immunol 1992 Nov
PMID:T cell receptor rearrangements in various S49 lymphoma sublines. 132 77

Isolated follicular dendritic cells (FDCs) showed true and pseudoemperipolesis of fresh tonsillar lymphocytes, even after long-term (50-day) cultivation. Emperipolesis by FDCs was not restricted by allotype specificity, nor was it inhibited by the addition of antibodies against MHC-I & II antigens. Follicular dendritic cells predominantly engulfed B-cells; monocytes and macrophages were not found between FDC cytoplasmic extensions. When highly purified T-cell populations were added to FDC cultures emperipolesis of T-cells occurred, particularly those of the CD4-positive phenotype. Mitoses appeared within 6 h in the emperipolesed lymphocytes and, after an additional 18 h, some lymphocytes exhibited apoptosis.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Emperipolesis of lymphoid cells by human follicular dendritic cells in vitro. 135 23

To understand better the specificity of peptide binding by MHC class I molecules, we have evaluated the capacity of a panel of unrelated peptides to compete for the presentation of viral peptides presented by HLA-A3 and HLA-B27. The HIV-Nef7F peptide (74-82) was presented by HLA-A3 to Nef-specific HLA-A3-restricted CTL lines, and the influenza nucleoprotein peptide NP(380-393) was presented by HLA-B27 to NP(380-393)-specific HLA-B27-restricted CTL lines. In addition, we have extended studies from our group that have evaluated the capacity of a similar panel of peptides to inhibit presentation of an influenza nucleoprotein peptide NP (335-349) by HLA-B37 and a matrix peptide, M1 (57-68), by HLA-A2 to the appropriate peptide-specific CTL lines. Out of 41 peptides tested, only five bound to more than one of the MHC molecules analyzed. Pairwise comparisons of the peptide binding specificities among these four different class I molecules revealed no common competitor peptides in four of the six possible comparisons. Thus, each class I molecule appears to have a functionally distinct peptide binding site, as reflected by the ability to bind largely non-overlapping sets of peptides.
Mol Immunol 1992 Sep
PMID:The peptide binding specificity of HLA class I molecules is largely allele-specific and non-overlapping. 137 81

Guanethidine sulphate causes destruction of peripheral sympathetic neurons and infiltration of mononuclear inflammatory cells in the sympathetic ganglia of both athymic nude (rnu/rnu) and euthymic LEW/Mol rats. The effect of guanethidine is believed to be an autoimmune reaction. To determine the effect of immunosuppressive drugs concurrently with guanethidine treatment both athymic and euthymic rats were treated with guanethidine 40 mg/kg i.p. daily for 14 days, cyclophosphamide 100 mg/kg i.p. on days 1 and 8, methylprednisolone 10 mg/kg and cyclosporin A 10 mg/kg daily from days 1 to 7, and then every other day from days 8 to 14. The number of neurons in the sympathetic ganglia was counted and four subpopulations of mononuclear inflammatory cells were identified by monoclonal antibodies MHC II, CD8 T-cells/NK-cells, CD5 T-cells, CD4 T-cells/macrophages. Our results show that the immunosuppressive drugs used were unable to prevent the guanethidine-induced reduction of sympathetic neurons, although the number, of neurons following guanethidine-methylprednisolone treatment was significantly higher compared with guanethidine alone in both athymic and euthymic rats. The identification of mononuclear cells in the sympathetic ganglia showed that the CD8/NK and CD5 populations were the populations primarily responding to guanethidine treatment. Both CD8/NK and CD5 populations were absent without guanethidine, but increased significantly following guanethidine in both athymic and euthymic animals. None of the immunosuppressive drugs used could prevent the guanethidine-induced rise in the CD8/NK population in neither athymic nor in euthymic rats. The rise in the CD5 population was suppressed following treatment with all immunosuppressive drugs in athymic rats, but only following methylprednisolone in euthymic animals. These results indicate that guanethidine induces proliferation of T-cells in euthymic rats and non-functional CD5 positive pre T-cells in athymic animals. The CD5 population in both athymic and euthymic animals appears relatively more sensitive to immunosuppressive drugs than the NK-cell population also activated by guanethidine. This relatively resistant NK-cell population seems to play an important role in the guanethidine-induced destruction of sympathetic neurons and can explain why the guanethidine-induced immunological reaction could not be fully prevented by the immunosuppressive drugs used. The conclusion is that guanethidine induces destruction of sympathetic neurons by a NK-cell-mediated reaction.
 ...
PMID:Effect of immunosuppressive agents on the guanethidine-induced sympathectomy in athymic and euthymic rats. 138 39

The genomic sequence of a 66,109 bp long region within the human MHC has been determined by manual and automated DNA sequencing. From cDNA mapping and sequencing data it is known that this region contains a cluster of at least four genes that are believed to be involved in antigen processing. Here, we describe the genomic organization of these genes, which comprise two proteasome-related genes (LMP2 and LMP7), thought to be involved in the proteolytic degradation of cytoplasmic antigens and two ABC transporter genes (TAP1 and TAP2), thought to be involved in pumping of the degraded peptides across the endoplasmic reticulum membrane. Analysis of the sequence homology and the intron/exon structures of the corresponding genes suggests that one gene pair arose by duplication from the other. Comparison of the available sequence data from other organisms shows striking conservation (70 to 84%) of this gene cluster in human, mouse and rat. The presence of several potential interferon stimulated response elements (ISREs) is in agreement with the experimentally observed up-regulation of these genes with gamma-interferon.
J Mol Biol 1992 Nov 20
PMID:DNA sequence analysis of 66 kb of the human MHC class II region encoding a cluster of genes for antigen processing. 145 54

In a protein antigen the number of epitopes that are presented by the MHC molecules to the T cells is generally limited. This phenomenon of immunodominance determines the T cell response to a given antigen. To understand the molecular basis of epitope selection we have analysed the hierarchy of T cell epitopes in a repeating synthetic polypeptide antigen Poly 18, Poly EYK(EYA)5 in the mice of H-2d haplotype. Because of its repeating nature, all the potential epitopes of Poly EYK(EYA)5 generated as a result of antigen processing will have extensive sequence overlap, therefore, providing an excellent system to investigate the molecular basis of T cell peptide epitope selection in vivo. We have synthesized a series of 12 and 15 amino acid peptides to mimic these epitopes. In H-2d mice Poly EYK(EYA)5 elicits T cell clones that optimally react with 15 amino acid peptides EYK(EYA)4 and/or (EYA)5. Similar results were obtained when related 12 amino acid peptides EYK(EYA)3 and/or (EYA)4 are used. (EYA)5 reactive T cell clones appear to be very heterogenous and much larger in number than EYK(EYA)4 reactive clones. (EYA)5 reactive clones could be elicited by at least three short Poly-18 derived epitopes (EYA)4, EYK(EYA)3 and (EYA)3EYK while EYK(EYA)4 reactive clones elicited only by the EYK(EYA)3 epitope. However, we observed the dominance of (EYA)5 reactive clones even when EYK(EYA)3 was used as an immunogen and this could be related to the degeneracy of their antigen specificity. Our earlier antigen competition studies suggest that (EYA)5 does not compete with EYK(EYA)4 epitope in binding to I-Ad. Therefore, there is no intramolecular competition between these epitopes to activate T cells. The epitope (EYA)3EYK appears to be subdominant since it can elicit Poly EYK(EYA)5 specific T cells upon immunization but does not appear to be part of Poly EYK(EYA)5 repertoire. Peptides such as (EYA)2EYKEYA or EYAEYK(EYA)2 with lysine substitution in the middle of the sequence were non immunogeneic. Similar results were obtained when the larger 15 amino acid peptides were used as antigen. Another level of epitope immunodominance is seen when substituted peptides of the two immunodominant epitopes are used. Some of these epitopes have potential to be part of the Poly 18 repertoire but they are greatly under represented when intact Poly 18 is used as antigen. The unusual hierarchy observed for immunodominance in these overlapping epitopes of EYK(EYA)5 sequence suggest a bias in the selection of T cell repertoire based upon the crossreactivity between potential epitopes generated as a result of antigen processing.
Mol Immunol 1992 Dec
PMID:Evidence for immunodominance between closely related epitopes in the selection of T cell repertoire: hierarchy of T cell epitopes in a repeating sequence. 145 65

In an attempt to define structures interacting with CD8 molecules during activation of CD8+ cells, immunoprecipitates of CD8 and Tcr-CD3 molecules from lysates of a surface-labeled CTL clone were analyzed. No proteins other than the known Tcr alpha/beta and associated CD3 components were detected in either anti-Tcr or anti-CD3 immunoprecipitates, whether or not the CTL clone had been activated. However, anti-CD8 antibodies co-precipitated class I MHC heavy chain and associated beta 2-microglobulin in all conditions. The latter co-precipitation was shown to result from "cis-type" interactions between CD8 and class I MHC proteins on the same cell and to involve a degree of selectivity, as class I MHC molecules were absent from immunoprecipitates of highly expressed cell surface molecules such as LFA-1. A further analysis of cell surface molecular distribution during antigen-dependent CTL-target cell interaction by double fluorescence-microscopy in non-activating conditions indicated that an increased density of CTL class I molecules was found in the CTL-target cell contact zone of most conjugates with redistributed CD8 molecules. A possible role for "cis-type" class I MHC-CD8 interactions in the dynamics of CTL-target cell contacts is proposed.
Mol Immunol 1991 Aug
PMID:Biochemical and functional association between CD8 and H-2 at the surface of a T cell clone. 167 58

Surgical specimens of lung cancers were examined immunopathologically for the expression of major histocompatibility complex class II (MHC-II) antigens in the tumor cells and their relationship to the lymphocytic infiltration. A lymphocytic infiltrate was frequently observed in the tumor tissue, though its intensity differed among the various histological types. MHC-II antigens were often demonstrated in tumors with a lymphocytic infiltrate. They were detected predominantly in the cytoplasm of tumor cells and to a lesser extent on the cell membranes. The emergence of the MHC-II-positive tumor cells was closely related to a local infiltration by lymphocytes including interferon-gamma (IFN-gamma)-producing T-cells. On the basis of the histological findings, an in vitro experiment was carried out. Four types of lung cancer cells were incubated with recombinant IFN-gamma in order to induce MHC-II antigens. MHC-II antigens (HLA-DR as well as HLA-DQ and HLA-DP antigens) were elicited in three cancer cell lines depending on the concentration of IFN-gamma. Immunoelectron microscopic study revealed that they were expressed on the surface of the cell membrane, though to a lesser extent than in the cytoplasm. It was considered that MHC-II antigens could be induced in some tumor cells in the immunological environment where IFN-gamma was secreted from T-cells and concentrated locally.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Expression of MHC class II antigens in human lung cancer cells. 168 57

CTLs (CD8+) are known to recognize exogenous peptide in the context of class I MHC molecules. We observed that an influenza subtype H1 and H2 cross-reactive CTL clone B7, which was stimulated by a fusion protein containing a portion of HA2 subunit of A/PR/8 virus HA, recognized a synthetic peptide (residues 515-526) of the HA2 subunit of A/PR/8 virus strain. This CTL clone also recognized a structurally disparate NS1 peptide 50-68 of the same A/PR/8 virus. We examined the recognition of the NS1 peptide 50-68 and the HA peptide 515-526 by the subcloned CTL clone, B7-B7. Cold target inhibition experiments showed that the recognition of the HA peptide by the CTL clone B7-B7 could be competed by NS1 peptide-treated target cells and vice versa. The recognition of both NS1 peptide and HA peptide by the CTL clone B7-B7 was restricted by the same allele, H2Kd. In addition, this NS1 peptide requires approximately a 600-fold higher concn for optimal CTL recognition than did the HA peptide. We conclude that the TCR on clone B7-B7 recognizes the HA peptide or the NS1 peptide as comparable complexes with the same class I MHC molecules, although there is no obvious homology in the primary sequences of HA 515-526 and NS1 50-68 peptides. CTLs elicited with certain antigens appear to recognize distinctively different antigens complexed to the same presenting MHC molecule.
Mol Immunol
PMID:Recognition of disparate HA and NS1 peptides by an H-2Kd-restricted, influenza specific CTL clone. 170 32


1 2 3 4 5 6 7 8 9 10 Next >>