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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antigenic competition is argued to impair the immune response on the level of accessory cell-dependent antigen presentation to responsive T-cells (regulated by MHC encoded Ir gene products). A possible influence of these mechanisms on in vivo immunization with antigen mixtures was investigated by using cytoplasmic extracts of four different strains of Escherichia coli as antigen sources for immunizing rabbits. The immune response against these antigen mixtures was tested by crossed immune electrophoresis (CIE) and immunoblotting (IB) in a homologous system (a given antigen extract of one strain against the corresponding antisera) and in the heterologous system (antigen extract of one strain against the antisera of different other strains). Several proteins were non-immunogenic in the extract of one strain but elicited good antibody responses in other strains. One of the strain-specific non-immunogenic proteins was purified and revealed a normal immune response upon immunization. The data suggest that different antigenic competition effects are induced by different protein compositions of antigen mixtures. This strain-specific competition seems to determine the immunogenicity of certain molecules (and not only the immunogenic properties of the molecules themselves). Furthermore this method offers a practical approach to increase the antibody production against weak immunogens in antigen mixtures.
Mol Immunol 1988 Mar
PMID:Antigenic competition in the immune response against protein mixtures: strain-specific non-immunogenicity of Escherichia coli antigens. 328 42

Nucleotide sequence analysis of mRNA from the H-2K locus of the CBA.M523 mouse, which has the class I murine MHC mutation H-2Kkml, has established the only alteration to be at the codon for amino acid position 152 as compared to the sequence of standard Kk from both the AKR and CBA inbred mouse lines. Complete sequence information for the nucleotides coding for amino acids 1-292, which includes all of the extracellular protein domains, demonstrated an A----C alteration in the codon for amino acid 152 as compared to the standard Kk sequence, changing Asp (GAT) in Kkml. The GCT codon occurring in Kkml may be the result of a gene conversion in Kkml. The GCT codon occurring in Kkml may be the result of a gene conversion event because a potential donor gene, the pH-2III pseudogene of H-2k, is transcribed in the CBA.M523 mouse and has a GCT codon at amino acid position 152. This sequence information obtained for Kkml also demonstrates that Kk gene transcripts from two genetically distinct inbred mouse lines, CBA and AKR, are completely identical. Finally, several other murine and human class I MHC variants have similar alterations at amino acid position 152 which result in altered biological functions. This information suggests that amino acid 152 is an important part of a T-cell-recognized antigenic determinant on MHC class I antigens.
Mol Immunol 1988 Mar
PMID:The H-2Kkml mutation: a single nucleotide substitution is responsible for multiple functional differences in a class I MHC molecule. 337 94

By typing a large quantity of family-based material for HLA-B, HLA-DR, C4, C2 and factor B, we were able to derive four-gene complement haplotypes (C4A, C4B, C2, BF) and six-gene MHC haplotypes (HLA-B, complement, HLA-DR). Fourteen six-gene MHC haplotypes showed linkage disequilibrium but exact frequencies could not be determined because it was not always possible to assign null C4 alleles in families where null genes were not clearly seen to segregate. Comparison of unrelated type I diabetes, Graves' disease and Hashimoto's thyroiditis patients with healthy unrelated controls revealed the following MHC allele associations: C4B*3, HLA-DR3 and HLA-DR4 with type I diabetes; BF*F1 and HLA-DR3 with Graves' disease; HLA-DR4 with Hashimoto's thyroiditis. By typing families of type I diabetes and Graves' disease patients we were able to derive two high-risk DR3+ MHC haplotypes for both type I diabetes and Graves' disease. These are HLA-B8 C4A*Q0 C4B*1 BF*S HLA-DR3 and HLA-B18 C4A*3 C4B*Q0 BF*F1 HLA-DR3, and these haplotypes account for most of the associations between these diseases and HLA-DR3. The MHC haplotype HLA-B15 C4A*3 C4B*3 BF*S HLA-DR4 also carries high risk for type I diabetes in this group of patients. Our data suggest that other DR4+ haplotypes, probably containing C4A*3 C4B*1, carry increased risk for type I diabetes whereas haplotypes containing DR4 and C4 C4A*3 C4B*Q0 do not. Our phenotype data suggest that DR4 in Hashimoto's thyroiditis is frequently associated with HLA-B44, C4A*3, C4B*1 and BF*S.
Mol Biol Med 1986 Apr
PMID:Class III alleles and high-risk MHC haplotypes in type I diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. 346 Dec 34

Graves' disease is associated with HLA-DR3 in Caucasoids. We have now demonstrated, on the basis of disease-associated MHC haplotypes (A1, Cw3, B8, DR3 and fragments thereof) from 38 families in which more than one member had Graves' disease compared with MHC haplotypes from 56 healthy families, that the risk was highest with the DR locus (relative risk for A1, B8, DR3 = 2.3, for B8, DR3 = 5.3, and for DR3 = 6.8). We further used the sib-pair method to explore linkage of Graves' disease liability to the MHC in 67 affected sib-pairs. The data were consistent with an MHC-linked recessive gene with a frequency of 0.2 to 0.3 and a penetrance of 7.2%; the data, however, accommodated penetrance of up to 16.3%. A recessive model was also consistent with the HLA-B8 genotype distribution in 286 unrelated patients. As the effect of the marker alleles on the course of the disease had been debated several times, we applied a cluster analysis method using 49 clinical and laboratory characteristics, including the HLA-A and HLA-B antigens of 196 patients. Three groups were identified, corresponding to patients with mild disease, Hashitoxicosis and severe (relapsing) disease. The prevalence of HLA-B8 was 8.9%, 21% and 87%, respectively (compared to 18.8% in 380 controls). This suggests the existence of an underlying continuum of genetic liability, apparently related to that for Graves' disease severity, associated with the MHC and mediated through immunoregulatory disturbances.
Mol Biol Med 1986 Feb
PMID:The role of HLA antigens in the manifestation and course of Graves' disease. 348 58

The T cell surface molecules Lyt-2 and L3T4 are strongly correlated with the class of MHC gene product recognized by the T cell bearing them. The L3T4 molecule has been proposed to play a role in enhancing recognition of antigen:Ia by specific T cells. In the present experiments, we have explored the role of L3T4 in T cell activation by examining the effects of the L3T4-specific monoclonal antibody GK1.5 on T cell responses in the presence or absence of class II-MHC gene products. Our studies show that GK1.5 inhibits T cell activation in the absence of class II-MHC gene products, while antibodies to other T cell surface molecules do not transduce negative signals to the same cells. We interpret our results as suggesting a signaling role for L3T4 and, by inference, for Lyt-2 as well. We would propose that L3T4 molecules on the class II-restricted T cell initiate the interaction between the L3T4+ T cell and its class II-MHC gene product bearing target cell (B cell, APC). This initial contact is important in allowing a finite time for antigen, Ia, and the T cell receptor to form an activating complex, which in turn transduces a dominant on signal to the cell. In the absence of specific antigen, or if the class II-bearing cell is of the wrong MHC genotype, so that the antigen:Ia receptor is not aggregated, then the association of L3T4 with class II molecules transduces a net negative signal to the T cell. We suggest that this negative signal is responsible for T cell:target cell deconjugation under these circumstances. Thus, we would propose that L3T4 initiates T cell:Ia-bearing cell interactions and, a finite time later, signals the T cell to discontinue the interaction unless a stimulating level of the antigen:Ia complexes for which the T cell's receptor is specific is present.
J Mol Cell Immunol 1986
PMID:The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal. 350 16

We have previously shown that activated T lymphocytes spontaneously internalize their own surface class I MHC antigens and that this phenomenon is specific for these cells since it does not occur in B lymphocytes even after activation. The present work was aimed at defining the quantitative aspects of this phenomenon and, in particular, at the elucidation of the route of the internalized class I MHC antigens. We intended to determine if the internalized molecules are delivered to the lysosomal compartment and digested there or if instead they are brought back to the plasma membrane in a recycling pathway similar to that described for various cell surface proteins known to be engaged in the process of receptor-mediated endocytosis. We have devised a flow cytometric assay based on the use of fluorochrome-labeled monoclonal anti-H-2K antibodies to measure the kinetics of H-2K internalization. Comparison of the time necessary for the internalization of one-half of the surface H-2K molecules in activated T lymphocytes, which is approximately 1 hour, with the half-life of these molecules on the same cells, which is 14 hours, clearly indicates that the internalized molecules are not degraded but are instead recycled. The recycling takes place in an endosomal compartment with an average pH of about 5.6. The monoclonal anti-H-2K antibody used in these studies was not eluted from the H-2K molecules at this pH and is recycled along with them. On the other hand, protein A bound to the Fc of the anti-H-2K antibody was eluted at the low pH of the endosomes, delivered to lysosomes, and digested. We have therefore defined a novel phenomenon, namely the recycling of class I MHC antigens, which occurs selectively in T lymphocytes. The features of this phenomenon are similar to the recycling of surface receptors which mediate the endocytosis of a variety of extracellular ligands in different cells. However, no physiological extracellular ligand is known for class I MHC antigens. It is a reasonable speculation that upon activation T lymphocytes recycle their own surface class I MHC antigens as part of the complex machinery whereby these lymphocytes recognize and respond to non-self moieties on the plasma membranes of presentor or target cells.
J Mol Cell Immunol 1986
PMID:Recycling class I MHC antigens: dynamics of internalization, acidification, and ligand-degradation in murine T lymphoblasts. 350 17

In the previous paper in this series, we described a form of self-reactivity among T cells called the "syngeneic T-T lymphocyte reaction" (STTLR). The phenomenon involves responder T cells that are stimulated to proliferate by irradiated antigen or self-reactive cloned T cell lines. The proliferative STTLR occurs in cultures rigorously depleted of conventional APC and is inhibitable by anti-Ia antibodies of the appropriate specificity. We also showed that both L3T4+ Lyt2- and L3T4- Lyt2+ T cell subsets participate in the STTLR-induced by the IEk-specific Lbd T cell line. In this paper, we report our studies on the effector phase of STTLRs, in particular, the cytotoxic responses induced by Lbd cells. We demonstrate that uncloned and cloned lines (called Dbl) of anti-Lbd cytotoxic cells are L3T4- Lyt2+ effector cells that kill Lbd, antigen-reactive T cells, and syngeneic B cells stimulated with LPS. They also kill syngeneic splenic cells stimulated with Con A for 72 h or less; longer culture periods in the presence of Con A yield Dbl-resistant T cells. Resting T cells are also resistant to Dbl cells. Using LPS-induced splenic B cells from H-2 congenic mice, we map the anti-self specificity of uncloned and cloned anti-Lbd cells to the Kk + IAk regions of the MHC. Seemingly concordant results were obtained using L transformants expressing IAk molecules on their surface. However, control studies with fibroblast lines and UV-induced fibrosarcoma cells unexpectedly revealed a high susceptibility to lysis by Dbl cells among certain Ia- cell lines. These results suggested that the antigen recognized by Dbl cells is not IAk itself but either an MHC-encoded or MHC-regulated gene product expressed by activated T and B cells and certain tumor cells. The target antigen is important in immunoregulation because Dbl cells suppress both the proliferation of Lbd cells to syngeneic cells and primary T cell-dependent anti-SRC PFC responses. From an immunoregulatory viewpoint, the existence of Lbd-Dbl cells offers several appealing features. Since Lbd cells cannot activate resting B cells or replace antigen-specific helper cells, they cannot initiate immune responses nonspecifically. In the presence of the appropriate antigen-specific helper T cells, Lbd and other self-reactive cells can amplify an immune response and thus facilitate its exponential growth. Since the self-reactive cells activate the Dbl cytotoxic circuit described above, they also provide the stimulus required to terminate immune responses quickly.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1986
PMID:The syngeneic T-T lymphocyte reaction (STTLR). II. Induction of primary T anti-T cell cytotoxic responses in vitro in T cell cultures stimulated with syngeneic self-reactive T cells. 350 19

B cell lymphomas which can be growth inhibited by crosslinking their surface IgM receptors by anti-Ig reagents provide models for normal B cell regulation and tolerance. WEHI-231 and CH31 are two independently derived lines that are exquisitely sensitive to negative signalling by antibodies specific for mu or kappa chains, but are unaffected by antibodies against MHC class 1 or 2 antigens. In order to determine the mechanism of this growth inhibition as a model for tolerance, we have examined the roles played by protein kinase C activation and calcium mobilization/influx during negative signalling in these cells. We found that growth inhibition caused by anti-mu crosslinking was reversed in the presence of either phorbol myristate acetate (PMA) or by lipopolysaccharide (LPS) from E. coli. The effect of PMA on negative signalling was a true reversal since phorbol esters could be added after anti-mu treatment, thus allowing nearly normal cellular progression into the S phase of the cell cycle. In contrast, pretreatment with PMA did not provide protection against the growth inhibition from anti-mu. Indeed, a "desensitization" protocol demonstrated that PMA pretreatment actually decreased reversal by both PMA and LPS of the effects of anti-mu on B lymphoma growth. These studies suggest that both LPS and PMA act via at least one common intermediate, which is assumed to involve activation and translocation of protein kinase C. Analysis of changes in calcium ion concentration after treatment with anti-Ig reagents showed both mobilization from internal stores and influx via calcium channels in WEHI-231, as has been reported for normal B cells. However, these changes did not correlate with negative signalling for the several reasons. Firstly, anti-mu inhibition of the growth of WEHI-231 could be induced in the relative absence of extracellular Ca++ or in quin-2 loaded (buffered) cells. Secondly, pretreatment with high concentrations of PMA ablated calcium mobilization, yet failed to modulate growth inhibition in WEHI-231 cells. Moreover, LPS provided protection from the effects of anti-mu yet did not alter cellular [Cai++]. In addition, PMA posttreatment (under conditions causing a reversal of the effects of anti-mu) can be applied as long as four hours after the initial exposure to anti-mu and the rapid measurable changes in calcium flux. Indeed, such changes in intracellular free calcium occurred in elutriated WEHI-231 lymphoma cells at all phases of the cell cycle, although we have previously identified early G1 as the only critical period in which negative signalling can be delivered.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1987
PMID:Lymphoma models for B cell activation and tolerance. V. Anti-Ig mediated growth inhibition is reversed by phorbol myristate acetate but does not involve changes in cytosolic free calcium. 350 21

Nucleotide sequence analysis of mRNA from the class I murine MHC mutant H-2Kkml has established a site of mutation to be at the codon for amino acid position 152. Complete sequence information for the nucleotides coding for amino acids 136-163 demonstrates an A----C alteration at the codon for amino acid 152, changing Asp (GAT) in Kk to Ala (GCT) in Kkml. Several other murine and human class I MHC variants have similar alterations at amino acid position 152, resulting in altered biological activity. Finally, the pH-2III pseudogene of the H-2k haplotype has a GCT codon at amino acid position 152, suggesting that the GCT codon occurring in Kkml is the result of a gene conversion event.
Mol Immunol 1987 Feb
PMID:The H-2Kkml mutation: nucleotide sequence and comparative analysis. 361 11

Balb/c mice were immunized with a human endothelial cell pool. Spleen cells were then fused with a NS-O hybridoma cell line. A number of hybridomas secreted antibodies that reacted with the immunizing endothelial cell pool as well as with every other tested umbilical cord vein derived human endothelial cell. These monoclonal antibodies also stained pig, rabbit and ox aortic endothelial cells indicating their specificity for this cell type. Five of 16 monoclonal antibodies additionally reacted with human fibroblasts (HFIB). The produced monoclonal antibodies did not recognize FVIIIR:AG or MHC determinants. They can therefore be regarded as additional and reliable markers for endothelial cells in vitro.
Mol Cell Biochem 1987 Jul
PMID:Mouse monoclonal antibodies specific for endothelial cells. 362 15


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