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At least 19 recordsLinked to original sources
PubMed1991

Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation.

A successful immune response requires intercellular contact between T and B lymphocytes. We recently showed that CD28, a T cell surface protein that regulates an activation pathway, could mediate intercellular adhesion with activated B cells by interaction with the B7 antigen. Here we show that CD28 is the primary receptor for B7 on activated peripheral blood T cells, that CD28 binds to B7 in the absence of other accessory molecules, and that interaction between CD28 and B7 is costimulatory for T cell activation. To characterize the binding of CD28 to B7, we have produced genetic fusions of the extracellular portions of B7 and CD28, and immunoglobulin (Ig) C gamma 1 chains. 125I-labeled B7 Ig bound to CD28-transfected Chinese hamster ovary (CHO) cells, and to immobilized CD28 Ig with a Kd approximately 200 nM. B7 Ig also inhibited CD28-mediated cellular adhesion. The function of CD28-B7 interactions during T cell activation was investigated with soluble fusion proteins and with B7-transfected CHO cells. Immobilized B7 Ig and B7+ CHO cells costimulated T cell proliferation. Stimulation of T cells with B7+ CHO cells also specifically increased levels of interleukin 2 transcripts. These results demonstrate that the CD28 signaling pathway could be activated by B7, resulting in increased T cell cytokine production and T cell proliferation. Cellular interactions mediated by B7 and CD28 may represent an important component of the functional interactions between T and B lymphoid cells.

Animals↗
PubMed1993

Effects of cyclosporin A, FK 506, and mycalamide A on the activation of murine CD4+ T cells by the murine B7 antigen.

The murine B7 (mB7) protein is a potent co-stimulatory molecule for the activation of murine CD4+ T cells. We have previously shown that stable mB7-transfected Chinese hamster ovary (CHO) cells synergize with either anti-CD3 monoclonal antibodies (mAb) or concanavalin A to stimulate T cell activation. In addition, mB7 can synergize with phorbol 12-myristate 13-acetate (PMA) to induce T cell activation in an alternative pathway. In the present report we describe the effects of three immunosuppressive drugs, cyclosporin A (CsA), FK 506, and mycalamide A on mB7-mediated T cell activation. The immunophilin ligands CsA and FK 506 block activation of murine CD4+ T cells by the combination of anti-CD3 mAb and CHO-mB7 cells but do not affect activation by CHO-mB7 cells and PMA. These results support the relevance of pharmacological studies of immunosuppressive compounds in the murine model prior to their application in man. In contrast to the effects of CsA and FK 506, mycalamide A blocks activation of murine CD4+ T cells by anti-CD3 mAb and mB7 as well as activation by mB7 and PMA. On a molar basis, mycalamide A appears to be at least 10-fold more potent than FK 506 which is 100-fold more potent than CsA. Because of its effects on multiple activation pathways and because of its potency, mycalamide A could have considerable therapeutic potential.

Animals↗
PubMed1995

Genomic organization of the gene coding for the costimulatory human B-lymphocyte antigen B7-2 (CD86).

The generation of an antigen-specific T-cell response requires that the T lymphocyte receive two signals from the antigen presenting cell. The specificity of this response is provided by antigen presented to the T lymphocyte and involves stimulation of the T lymphocyte via the T-cell receptor (TCR)/CD3 complex. The second, or costimulatory signal, can be provided by ligation of the B-lymphocyte activation antigens B7-1 (CD80) and B7.2 (CD86) to TCR antigen CD28. The cDNAs for both CD80 and CD86 have been isolated and are predicted to encode type 1 membrane proteins of the immunoglobulin (Ig) superfamily. The predicted protein is composed of a signal peptide followed by two Ig-like extracellular domains, a transmembrane domain, and a cytoplasmic tail. Here we report that the genomic organization of CD86 reflects its functional structure, and is similar to that found for CD80. The gene is composed of eight exons which span more than 22 kilobases. The predicted protein functional domains of signal peptide, extracellular IgV- and IgC-like regions, and transmembrane domain coincide with the genomic structure. Two independent sequences had been reported for CD86 cDNA which differed in their 5'untranslated (UT) regions. We find CD86 exons 1 and 2 correspond to these alternate 5'UT sequences. Splicing of exon 1 or 2 with the signal peptide encoding exon 3 would produce mRNA transcripts complementary to the reported cDNA clones. Exons 4 and 5 correspond to IgV- and IgC-like extracellular domains, respectively. Exon 6 encodes the transmembrane region and beginning of the cytoplasmic tail. Exons 7 and 8 encode the remainder of the cytoplasmic tail and 3'UT sequences.

Amino Acid Sequence↗
PubMed1992

Genomic organization and chromosomal location of the human gene encoding the B-lymphocyte activation antigen B7.

The human B lymphocyte activation antigen B7 provides regulatory signals for T lymphocytes as a consequence of binding to its ligands CD28 and CTLA-4. The cDNA for B7 has previously been isolated and predicted to encode a type I membrane protein. The predicted polypeptide has a secretory signal peptide followed by two contiguous Ig-like domains, a hydrophobic transmembrane region and a short cytoplasmic tail. Here we report the exon-intron genomic organization of human B7 and the chromosomal location. The gene has six exons that span approximately 32 kilobases of DNA. Exon 1 is not translated and the second exon contains the initiation ATG codon and encodes a predicted signal peptide. This gene structure is characteristic for several eukaryotic genes with tissue-specific expression. The third and fourth exons correspond to two Ig-like domains whereas the fifth and sixth exons encode respectively the trans-membrane portion and the cytoplasmic tail. This close relationship between exons and functional domains is a characteristic feature of genes of the Ig superfamily. Cell surface expression of the B7 gene product has previously been mapped to human chromosome 12 by antibody reactivity with the B7-specific monoclonal antibody BB-1. We here demonstrate that the B7 gene is located to the q21-qter region of chromosome 3 by DNA blot analysis of human x rodent somatic cell hybrids.

Amino Acid Sequence↗
PubMed1976

The prognostic value of HLA-B12 and HLA-B7 antigens in patients with increased intraocular pressure.

The presence of the histocompatibility antigens HLA-B12 or HLA-B7 in 76 patients with increased intraocular pressure and a GG response to topical corticosteroids (intraocular pressure over 31 mm Hg after six weeks of topical 0.1% dexamethasone eyedrops, four times daily) correlated with the development of glaucomatous visual field loss. In close agreement with prevalences in patients with primary open-angle glaucoma, 14 (88%) of the 16 patients with increased intraocular pressure and a GG response who developed glaucomatous visual field loss had either HLA-B12 or B7 antigens. Fourteen (41%) of 34 patients with increased intraocular pressure and a GG response who had B12 or B7 antigens developed glaucomatous visual field loss but only two (5%) of 42 similar patients without either antigen had visual field loss. Other factors such as the initial intraocular pressure, the horizontal cup/disk ratio, and family history of glaucoma proved less valuable as prognostic indicators in this series.

Adrenal Cortex Hormones↗
PubMed1984

Structural analysis of an HLA-B7 antigen variant detected by cytotoxic T lymphocytes.

It has been demonstrated previously that lymphocytes of donor CF (HLA-A29,w33; B7,14) are not recognized by the HLA-B7-specific CTL clone HG-31. This report presents a structural comparison of the HLA-B7 antigen of donor CF with a "normal" HLA-B7 antigen, derived from the cell line JY. Isoelectric focusing showed that CF HLA-B7 heavy chains were more acidic than JY HLA-B7 heavy chains by the equivalent of a single charge. High pressure liquid chromatography and ion exchange chromatography comparisons of double-labeled tryptic peptides revealed a single detectable difference, which corresponded to the tryptic peptide spanning residues 112 to 121 on the HLA-B7 heavy chain. Although the complete amino acid sequence of this peptide was not obtained, the partial sequence indicates a substitution of an unidentified amino acid for tyrosine at position 116 of the heavy chain. This residue is found to vary among HLA specificities and to be altered in many H-2Kb mutants.

Amino Acid Sequence↗
PubMed1991

Structure, expression, and T cell costimulatory activity of the murine homologue of the human B lymphocyte activation antigen B7.

Following occupancy of the T cell receptor by antigen, T cell proliferation and lymphokine production are determined by a second costimulatory signal delivered by a ligand expressed on antigen presenting cells. The human B cell activation antigen B7, which is expressed on antigen presenting cells including activated B cells and gamma interferon treated monocytes, has been shown to deliver such a costimulatory signal upon attachment to its ligand on T cells, CD28. We have cloned and sequenced the murine homologue of the human B7 gene. The predicted murine protein has 44% amino acid identity with human B7. The greatest similarity is in the Ig-V and Ig-C like domains. Murine B7 mRNA was detected in murine hematopoietic cells of B cell but not T cell origin. Cells transfected with murine B7 provided a costimulatory signal to human CD28+ T lymphocytes. These results demonstrate the costimulatory activity of murine B7 and provide evidence that the ligand attachment site is conserved between the two species.

Amino Acid Sequence↗
PubMed1983

HLA-A2 and HLA-B7 antigens are phosphorylated in vitro by rous sarcoma virus kinase (pp60v-src) at a tyrosine residue encoded in a highly conserved exon of the intracellular domain.

HLA-A2 and -B7 antigens are phosphorylated by Rous sarcoma kinase (pp60v-src) in vitro. The phosphate group is attached to the heavy chains as determined by NaDodSO4/polyacrylamide gel electrophoresis. The site of phosphorylation was localized to the COOH-terminal intracellular domain by its susceptibility to limited trypsin proteolysis. Furthermore, the 32P-labeled amino acid is a single tyrosine residue located in the COOH terminus of the heavy chain. The protein sequences of known class I human and murine intracellular domains contain a highly conserved sequence -K-G-G-X-Y- located NH2-terminally to the single tyrosine residue of this domain. The DNA sequences that encode class I antigen intracellular domains were compared by computer with a homology matrix program. Exon 6 which encodes the conserved tyrosine-containing protein sequence in both human and mouse is 75% homologous across species and 90-100% homologous within species. The significance of the high degree of conservation within exon 6 is discussed.

Amino Acid Sequence↗
PubMed1988

Epitope mapping of HLA-B27 and HLA-B7 antigens by using intradomain recombinants.

To study the HLA-B7 and HLA-B27 antigenic determinants, hybrid genes between these two alleles were constructed by in vivo recombination in Escherichia coli. After transfection of these genes into P815 (high transfection efficiency recipient) murine cells, the bindings of Bw6, HLA-B7, and HLA-B27 allele-specific mAb were studied, as well as that of human anti-HLA-B7 and anti-HLA-B27 monospecific alloantisera. Most of the HLA-B7 antigenic determinants were assigned to the first external domain of the molecule. Four different epitopic areas could be defined: the Bw6 epitope was associated with residues 82 and 83; the BB7.1 epitope to amino acids 63, 67, and 70; the MB40.2 and MB40.3 epitope to amino acid sequence 177-180, and human alloantisera identified as an epitope associated with residue 9. HLA-B27 antigenicity studied by TM-1 mAb was found to involve residues 77 and 80 in the alpha-1 domain. Results obtained with human monospecific alloantisera allowed the definition of an additional allospecific site associated with the NH2 terminal part on the alpha-1 domain of HLA-B27. Epitope mapping fits with data obtained by sequence comparisons and is discussed with reference to the crystallographic three-dimensional structure of the HLA-A2 molecule.

Amino Acid Sequence↗
PubMed1983

Association of human leukocyte antigens B7 and BW35 with sperm antibodies.

One hundred three infertile couples and 50 fertile couples were tested for the presence of sperm antibodies by passive hemagglutination and cytotoxicity assays and typed for human leukocyte antigens (HLAs) of the A and B loci. Fifty-four percent of the males and 43% of the females with sperm antibodies were found to have the HLA-B7 antigen, in contrast to 19% of a general population (P less than 0.0001). HLA-BW35 (a Workshop antigen of the B locus) was also present at a significantly increased antigenic frequency (P less than 0.00001) in those females with sperm antibodies. Of the 73 infertile couples with sperm antibodies, 79% shared the B7, B8, and/or BW35 alleles. Two of 12 infertile couples and 10 of 50 fertile couples without sperm antibodies shared these alleles. The significant association of HLA-B7 and BW35 alleles with sperm antibodies in infertile subjects suggests a selective disadvantage of these antigens in human reproduction.

Adult↗
PubMed1990

mAb 104, a new monoclonal antibody, recognizes the B7 antigen that is expressed on activated B cells and HTLV-1-transformed T cells.

A new monoclonal antibody (mAb) of the IgG1 subclass, mAb 104, has been obtained after immunization of mice with the Burkitt lymphoma cell line Jijoye. It only weakly binds to a small proportion of non-activated normal B cells and binds to a larger proportion of in vitro-activated normal B cells. All tested Epstein-Barr virus (EBV)-transformed B-cell lines, Burkitt lymphoma cell lines and freshly isolated follicular B-lymphoma cell preparations strongly bound mAb 104. mAb 104 did not bind to peripheral monocytes or tested myelomonocytic cell lines, or to resting and activated normal T cells, T-cell lines and T-cell clones. However, the recognized antigen is expressed on HTLV-1-infected T-cell lines and HTLV-1-transformed T-cell clones. mAb 104 immunoprecipitates, from Jijoyce cell lysates, a single polypeptide with an apparent MW of 45,000-60,000 and an isoelectric point of 5.6. Competition studies with the anti-B7 antibody (Freedman et al., 1987) demonstrated that mAb 104 and the anti-B7 block each others' binding. Furthermore, mAb 104 binds to transfected COS cells (Freedman et al., 1989) expressing the B7 antigen. Thus mAb 104 and and anti-B7 define the same antigen. The restricted distribution of the 104/B7 antigen to activated B cells and HTLV-1-transformed T cells may make it a useful marker for the study of pathological states linked to lymphocyte activation and for the functional study of B-cell subpopulations.

Antibodies, Monoclonal↗
PubMed1993

Accessory and alloantigen-presenting cell functions of A431 keratinocytes that stably express the B7 antigen.

Because keratinocytes are tolerogenic antigen-presenting cells (APC), we investigated the role of B7/BB-1 in reconstituting defective accessory cell (AC) and APC functions by such nonlymphoid cells. KC were induced to stably express B7/BB-1 by DNA-mediated gene transfection. This single-transformed B7/BB-1+ A431 cell line (but not control A431) functioned as AC for lectin-induced T-cell proliferation, as well as oxidative mitogenesis. This costimulation was dependent on B7/BB-1 expression since the monoclonal antibody BB-1 blocked costimulation of PHA mitogenesis by 75%. After the induction of class II MHC antigen expression by interferon-gamma, B7/BB-1+ KC but not control KC presented alloantigens to resting T-cells in the primary mixed lymphocyte reaction. These data indicate that the stable expression of B7/BB-1 antigen by KC reconstitutes defective AC and alloantigen-presenting activity. The lack of expression of such second signal by normal KC may be responsible for their ability to induce clonal anergy in vitro and in vivo.

Antigen-Presenting Cells↗
PubMed1991

B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2.

Occupancy of the T-cell receptor complex does not appear to be a sufficient stimulus to induce a T-cell-mediated immune response. Increasing evidence suggests that cognate cell-cell interaction between an activated T cell and an antigen-presenting cell may provide such a stimulus. A candidate T-cell surface molecule for this costimulatory signal is the T-cell-restricted CD28 antigen. Following crosslinking with anti-CD28 mAb, suboptimally stimulated CD28+ T cells show increased proliferation and markedly increased secretion of a subset of lymphokines. Recently, the B-cell surface activation antigen B7 was shown to be a natural ligand for the CD28 molecule, and both B7 and CD28 are members of the immunoglobulin superfamily. Here we report that B7-transfected CHO cells can induce suboptimally activated CD28+ T cells to proliferate and secrete high levels of interleukin 2. The response is identical whether T cells are submitogenically stimulated with either phorbol myristate acetate or anti-CD3 to activate the T cells. This response is specific and can be totally abrogated with anti-B7 monoclonal antibody. As has previously been observed for anti-CD28 monoclonal antibody, B7 ligation induced secretion of interleukin 2 but not interleukin 4. We have previously demonstrated that B7 expression is restricted to activated B lymphocytes and interferon gamma-activated monocytes. Since these two cellular populations are involved in antigen presentation as well as cognate interaction with T lymphocytes, B7 is likely to represent a central constimulatory signal that is capable of amplifying an immune response.

Animals↗
PubMed1977

The prevalence of HLA-B12 and HLA-B7 antigens in primary open-angle glaucoma.

HLA-B12 antigen was found in 50% and HLA-B7 was present in 49% of patients with primary open-angle glaucoma. Either one of the antigens B12 or B7 was noted in 88% of such glaucoma patients. The prevalences of B12, B7, or of either antigen were much greater in patients with primary open-angle glaucoma than in the general population or in patients with normal intraocular pressure. The prevalences in patients with ocular hypertension (IOP greater than 20 mm Hg) were intermediate between the ocular normotensives and the patients with primary open-angle glaucoma. The close association between HLA-B12 and HLA-B7 and primary open-angle glaucoma suggested immunologic components of the disease and possible convenient genetic markers.

Glaucoma↗
PubMed1987

The ability of cytotoxic T cells to recognize HLA-A2.1 or HLA-B7 antigens expressed on murine cells correlates with their epitope specificity.

Two groups of human and murine cytotoxic T lymphocyte (CTL) clones specific for human leukocyte antigen (HLA)-A2 or -B7 can be distinguished based on their ability to kill murine transfectants expressing these molecules. The clones which do not recognize murine transfectants exhibited greatly reduced conjugate formation with these cells, indicating that the inability to lyse these cells occurs in recognition and binding. No systematic differences in inhibitory titer between the two types of CTL clones were seen with anti-CD8 (Lyt-2), anti-LFA-1, or monoclonal antibodies against HLA class I molecules. However, blocking with anti-HLA class I monoclonal antibodies suggested that different CTL clones recognized spatially separate epitopes on HLA-A2 and -B7. In addition, a correlation between the inability to recognize murine transfectants and fine specificity was seen. Eight of nine clones which did not lyse murine transfectants also failed to recognize human cells expressing HLA-A2.2 or -A2.3. In contrast only 5 of 12 clones which lysed transfectants failed to recognize the variant molecules. Analogous data were obtained with human CTL clones raised against HLA-A2.1. These findings suggest that CTL clones that do not lyse murine cells expressing appropriate antigens recognize epitopes that have been altered or lost as a consequence of expression on the murine cell surface. It is suggested that the loss of HLA-associated epitopes on the murine cell surface may be due to differences between mouse and human cells in the processing or presentation of class I-associated peptides.

Animals↗
PubMed1991

Direct helper T cell-induced B cell differentiation involves interaction between T cell antigen CD28 and B cell activation antigen B7.

Cognate interactions between major histocompatibility complex class II antigen (Ag)-reactive CD4+ T helper (Th) and Ag-presenting B cells induce first the activation of B cells and their subsequent differentiation into Ig-secreting cells (IgSC). The Th cell-associated homodimeric glycoprotein CD28 has been implicated as an important regulator of Th activation. Recently, B cell-associated early activation Ag B7 has been identified as a ligand for the CD28 molecule. In this study, we have examined using monoclonal antibodies (mAb) the roles of CD28 and B7 molecules during the Th-B cell cognate interactions leading to the differentiation of B7+ B cells. Anti-CD28 mAb 9.3 specifically inhibited proliferative responses of CD4+ T cells to both allogeneic B cells and soluble Ag-presenting autologous non-T cells. In addition, anti-CD28 mAb 9.3 inhibited Th-induced differentiation of alloantigen-presenting B cells into ISC. Similar inhibition of both Ag-induced Th activation and B cell differentiation into ISC was observed using mAb BB1 which recognizes a B cell-associated molecule B7. In contrast, non-cognate Th-independent exogenous interleukin 6-induced differentiation of B7+ B cells into ISC was not inhibited by mAb to either molecule. These results clearly demonstrate the involvement of CD28 on Th and its ligand B7 on B cells during cognate Th-B interactions leading to the differentiation of B cells. Furthermore, these results also suggest the development of new mAb-based therapeutic approaches for exaggerated B cell activation associated with certain autoimmune diseases such as systemic lupus erythematosus.

Antigens, CD↗
PubMed2005

Lack of association of human leukocyte antigen-B7 with COPD and rate of decline in lung function.

BACKGROUND: Although variation in the human leukocyte antigen (HLA) locus is associated with various diseases, there have been a limited number of studies that have examined the possible role of HLA in chronic obstructive pulmonary disease (COPD). Only HLA-B7 has been shown to be correlated with low forced expiratory volume in 1s (FEV1) in Caucasians; however, this finding has not been replicated. The aim of this study was to investigate the contribution of the HLA-B7 allele to COPD and to rate of decline of lung function. METHODS: We determined the prevalence of HLA-B7 in a group of COPD patients and a non-obstructed control group of smokers by using a polymerase chain reaction-based genotyping assay. We also determined the prevalence of HLA-B7 in smokers selected from the National Heart Lung and Blood Institute, Lung Health Study for having the fastest and slowest decline of lung function. RESULTS: No significant difference was found in the frequency of HLA-B7 between the COPD and non-obstructed groups. There was also no significant association of HLA-B7 with rate of decline of lung function. CONCLUSION: These data indicate that HLA-B7 does not contribute to COPD or rate of decline of FEV1 in smokers.

Aged↗