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PubMed1990

Predicting antigenic determinants of autoantigens.

Predicting antigenic determinants of foreign proteins from their amino acid sequence and/or conformation is of growing importance in the production of synthetic vaccines and antigens. Unlike foreign antigenic proteins, little is known of the suitability of predictive techniques for defining antigenic regions of self proteins recognised by autoantibodies. In this study we describe our use of two computer programmes (HYDRO 3 and ACROPHILICITY [ACRO], Hopp, 1986) for the prediction of antigenic determinants of autoantigens of the cell nucleus. Using the amino acid sequence of the protein, HYDRO 3 and ACRO respectively, provide information on the hydrophilic and surface regions of the protein. Both methods were used to predict the antigenic determinants of known autoantigens, including histones, the A, B", E and 70 kD proteins of snRNPs, SS-B/La, proliferating cell nuclear antigen (PCNA) and others. Our analysis of the antigenic determinants of histones agreed with other studies which have used antihistone antibodies and fragments of histones to show that autoantibody reactive sites reside in the terminal portions of these proteins, particularly the amino terminus. A detailed study of histone 2B correctly identified most regions recognised by antibodies, particularly autoantibodies. In addition the recently described epitope of the autoantigen ribosomal protein P2 was predicted by this analysis. From these observations we hypothesize that linear antigenic sites of self proteins can be predicted. Our hypothesis can be proven experimentally by demonstrating specific interaction between autoantibodies and synthetic peptides homologous with the predicted determinant.

Autoantigens↗
PubMed1993

Reactivity and intracellular location of the ACTH cell autoantigen in human fetal and adult anterior pituitary tissue.

Autoantibodies to anterior pituitary ACTH cells have been described in the sera from patients with Cushing's disease. We were here able to show that true ACTH cell autoantibodies do not react with the hormone itself or with Fc receptors in ACTH cells. They rather recognize a distinct pituitary cell-specific cytoplasmatic autoantigen located in a juxtanuclear position. ACTH cells from human adult pituitaries express Fc receptors producing a non-specific broad and diffuse cytoplasmic binding of normal immunoglobulins. After preparation of Fc-free F(ab)2 fractions from human immunoglobulins it could be demonstrated by immunohistochemical methods that human adult pituitary ACTH cells also contain the fetal ACTH cell autoantigen. However, Fc receptors, ACTH hormone or other proopiomelanocortin- (POMC-) derived fragments and the ACTH cell autoantigen are all located at distinct intracellular sites. ACTH cells in human fetal pituitaries were shown to lack Fc receptors. Thus, with this source of antigen the characteristic autoantibody pattern can be detected with undigested sera.

Adrenocorticotropic Hormone↗
PubMed1994

Enhanced transcription of the gene encoding the SmN autoantigen in patients with systemic lupus erythematosus does not result in enhanced levels of the SmN protein.

The SmN, protein is closely related to the constitutively expressed SmB and SmB' autoantigens and can also act as a target for human autoimmune sera. In contrast to the single gene encoding SmB and SmB' which is expressed in all tissues, the distinct gene encoding SmN is expressed at high levels only in brain and heart tissue. We show that the SmN gene is transcribed at significantly elevated levels in peripheral blood mononuclear cells (PBMCs) from SLE patients compared to normal controls. In contrast no significant elevation in transcription of the genes encoding SmB/B' or the U1-associated 70kD RNP autoantigen is observed in these patients. The elevation in SmN gene transcription in patient PBMCs does not result however, in enhanced levels of the SmN protein in the PBMCs of these patients. The significance of transcriptional and post-transcriptional processes in regulating the expression in SLE patients of SmN and other autoantigens is discussed.

Adult↗
PubMed2000

Revisiting tolerance induced by autoantigen in incomplete Freund's adjuvant.

Injection of autoantigens in IFA has been one of the most effective ways of preventing experimental, T cell-mediated, autoimmune disease in mice. The mechanism that underlies this protection has, however, remained controversial, with clonal deletion, induction of suppressor cells or of type 2 immunity being implicated at one time or another. Using high resolution enzyme-linked immunospot (ELISPOT) analysis, we have revisited this paradigm. As models of autoimmunity against sequestered and readily accessible autoantigens, we studied experimental allergic encephalomyelitis, induced by myelin oligodendrocyte glycoprotein, proteolipid protein, myelin basic protein, and renal tubular Ag-induced interstitial nephritis. We showed that the injection of each of these Ags in IFA was immunogenic and CD4 memory cells producing IL-2, IL-4, and IL-5, but essentially no IFN-gamma. IgG1, but not IgG2a, autoantibodies were produced. The engaged T cells were not classic Th2 cells in that IL-4 and IL-5 were produced by different cells. The IFA-induced violation of self tolerance, including the deposition of specific autoantibodies in the respective target organs, occurred in the absence of detectable pathology. Exhaustion of the pool of naive precursor cells was shown to be one mechanism of the IFA-induced tolerance. In addition, while the IFA-primed T cells acted as suppressor cells, in that they adoptively transferred disease protection, they did not interfere with the emergence of a type 1 T cell response in the adoptive host. Both active and passive tolerance mechanisms, therefore, contribute to autoantigen:IFA-induced protection from autoimmune disease.

Adoptive Transfer↗
PubMed2000

Autoantigen-specific CD4+CD28low T cell subset prevents autoimmune exocrinopathy in murine Sjögren's syndrome.

Organ-specific autoimmune exocrinopathy resembling Sjögren's syndrome (SS) that spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is dependent on Th1-type CD4+ T cells. We previously reported that a cleavage product of 120-kDa alpha-fodrin may be an important autoantigen in the pathogenesis of SS in both an animal model and the patients. We demonstrate that in an animal model of SS with overt exocrinopathy, a unique CD4+ T cell subset expressing CD28low is dramatically increased in spleen cells before the disease onset, but that the CD4+ T cells of diseased mice were virtually all CD28high. We found that the spleen cells in these mice before the disease onset showed a significant increase in autoantigen-specific T cell proliferation. Analysis of in vitro cytokine production by spleen cells indicated, before the disease onset, severely impaired production of IL-2 and IFN-gamma in the animal model, whereas high levels of IL-4 were observed. Expression of cytokine genes, including IL-4, IL-10, and TGF-beta, was detected in FACS-sorted CD4+CD28low T cells by RT-PCR analysis. Transfer of CD4+CD28low T cells into the animal model actually prevented the development of autoimmune lesions including autoantibody production. These results suggest that a CD4+CD28low T cell subset that is continuously activated by an organ-specific autoantigen may play a regulatory role in the development of organ-specific autoimmune disease in an animal model of SS.

Adoptive Transfer↗
PubMed2002

Two distinctly HLA-associated contiguous linear epitopes uniquely expressed within the islet antigen 2 molecule are major autoantibody epitopes of the diabetes-specific tyrosine phosphatase-like protein autoantigens.

The related tyrosine phosphatase-like proteins islet Ag (IA)-2 and IA-2beta are autoantigens of type 1 diabetes in humans. Autoantibodies are predominantly against IA-2, and IA-2-specific epitopes are major autoantibody targets. We used the close homology of IA-2 and IA-2beta to design chimeras and mutants to identify humoral IA-2-specific epitopes. Two major IA-2 epitopes that are absent from the related autoantigens IA-2beta and IA-2Delta 13 splice variant ICA512.bdc were found contiguous to each other within IA-2 juxtamembrane amino acids 611-620 (epitope JM1) and 621-630 (epitope JM2). JM1 and JM2 are recognized by sera from 67% of patients with IA-2 Abs, and relatives of patients with type 1 diabetes having Abs to either JM epitope had a >50% risk for developing type 1 diabetes within 6 years, even in the absence of diabetes-associated HLA genotypes. Remarkably, the presence of Abs to one of these two epitopes was mutually exclusive of the other; JM2 Abs and not JM1 Abs were found in relatives with HLA DR3/4, DR4/13, or DR1/4 genotypes; and the binding of autoantibodies to the JM2 epitope, but not the JM1 epitope, markedly affected proteolysis of IA-2. This is a unique demonstration of HLA-associated B cell responses to epitopes within a single autoantigen in humans and is consistent with modification of Ag processing by specific Ab-influencing peptide presentation by HLA molecules.

Antigen-Antibody Reactions↗
PubMed2003

Ultraviolet B radiation-induced cell death: critical role of ultraviolet dose in inflammation and lupus autoantigen redistribution.

The nuclear self-Ags targeted in systemic lupus erythematosus translocate to the cell membrane of UV-irradiated apoptotic keratinocytes and may represent an important source of self-immunization. It is hard to understand how the noninflammatory milieu accompanying most apoptosis might provoke an immunogenic response leading to autoantibodies. We have found that the precise amount of keratinocyte UV exposure is crucial in determining the rate of apoptosis, the amount of inflammatory cytokine production, and the degree of autoantigen translocation. Low doses of UVB (</=15 mJ/cm(2)) promptly induced a normal, caspase-dependent apoptosis, while intermediate doses of UV-B (35 mJ/cm(2)) caused apoptosis with altered morphology, slower DNA fragmentation, and poly(ADP-ribose) polymerase degradation accompanied by increased Bcl-2. High doses of UVB (80 mJ/cm(2)) induced instead necrosis. We observed IL-1 production upon intermediate and high UVB doses. Nuclear Ag redistribution was also markedly UV dose dependent: at low doses, Sm, Ku, and DNA translocated to the surfaces of early apoptotic cells. At intermediate doses, these Ags concentrated on the cell membrane when the nucleus was still visible. At high doses, these autoantigens diffused into the cytoplasm and were released into the supernatant. Taken together, the results show that low-dose UVB induces prompt noninflammatory apoptosis. In contrast, intermediate and high doses of UVB induce proinflammatory apoptosis and necrosis, where the production of inflammatory cytokines is accompanied by exposure and release of autoantigens. The key importance of the UV dose on the fate of apoptotic keratinocytes and on their potential immunogenicity should help clarify the role of UVB in inducing systemic lupus erythematosus autoimmunity.

Antigens, Nuclear↗
PubMed2004

A major B cell epitope present on the apoptotic but not the intact form of the U1-70-kDa ribonucleoprotein autoantigen.

Apoptotically modified forms of autoantigens have been hypothesized to participate in lupus immunopathogenesis. This study identifies a major B cell epitope present on the apoptotic but not the intact form of the U1-70-kDa ribonucleoprotein lupus autoantigen (70k). Human autoimmune sera with strong recognition of apoptotic 70k and minimal recognition of intact 70k were identified and tested for reactivity to truncated forms of 70k by immunoblot and ELISA. Patient sera that preferentially recognized apoptotic 70k were specific for an epitope dependent on residues 180-205 of the protein. This epitope was also recognized by 19 of 28 (68%) intact anti-70k-positive autoimmune human sera with Abs also recognizing apoptotic but not the intact form 70k, but only 1 of 9 (11%) intact 70k-positive sera without such Abs (Fisher's exact, p = 0.0055). Immunization of HLA-DR4-transgenic C57BL/6 mice with a peptide containing this epitope induced anti-70k immunity in 13 of 15 mice, including Abs recognizing apoptotic but not intact forms of autoantigens in 12 of 15 mice. Anti-70k responder mice also developed spreading of immunity to epitopes on the endogenous form of 70k, and proliferative lung lesions consistent with those described in patients with anti-70k autoimmunity. Thus, a major epitope in the B cell response to U1-70 kDa localizes to the RNA binding domain of the molecule, overlaps with the most common T cell epitope in the anti-70k response, and is not present on the intact form of the 70k molecule. Immunization of mice against this epitope induces an immune response with features seen in human anti-70k autoimmune disease.

Animals↗
PubMed2006

The Sjogren's syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death.

Patients affected by Sjögren's syndrome and systemic lupus erythematosus (SLE) carry autoantibodies to an intracellular protein denoted Ro52. Although the serologic presence of Ro52 autoantibodies is used clinically for diagnostic purposes, the function of the protein or why it is targeted as an autoantigen in several rheumatic conditions has not been elucidated. In this study, we show that the expression of Ro52 is significantly increased in PBMC of patients with Sjögren's syndrome and SLE, and demonstrate that Ro52 is a RING-dependent E3 ligase involved in ubiquitination. Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway. The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability. These findings suggest that the increased expression of the Ro52 autoantigen in patients may be directly involved in the reduced cellular proliferation and increased apoptotic cell death observed in Sjögren's syndrome and SLE, and may thus contribute to the autoantigenic load and induction of autoimmune B and T cell responses observed in rheumatic patients.

Amino Acid Sequence↗
PubMed2002

Autoantigens and immune pathways in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a major systemic autoimmune disease. A plethora of putative autoantigens has been described by the reactivity of antibodies present in the sera of patients. Despite this there is little evidence implicating most of them in its pathogenesis. Autoantigens fall into two major groups: first, those that are associated with the joint, such as collagen type II, human chondrocyte glycoprotein 39, and proteoglycans, for which a pathogenic role is easily understood; and second, those proteins not associated with the joint. Of these there are three groups: (1) highly conserved foreign antigens with human homologues, such as heat shock proteins (HSPs), in which the initiating antigenic stimulus may be through infection; (2) post-translationally altered proteins, such as citrullinated filaggrin, to which autoantibodies show high specificity but low sensitivity for RA and immunoglobulin G; and (3) ubiquitous proteins, such as glucose-6-phosphate isomerase, p205, and HSPs secreted during stress, such as BiP. The mechanisms by which such ubiquitous antigens cause pathology predominantly in the joints are difficult to understand. Autoantibodies, such as rheumatoid factors, that form immune complexes resulting in activation of phagocytic cells or the complement system, may cause joint pathology by deposition in the joints. Such an explanation, however, is not available for all of these autoantigens. It is possible that pathology may be the outcome of disturbed immunoregulation.

Arthritis, Rheumatoid↗
PubMed1991

Presentation of autoantigen by human T cells.

Activated human T cells express MHC class II and have been shown to present foreign Ag to autologous T cells. We now demonstrate that MHC class II+ T cell clones can present myelin basic protein (MBP) peptide autoantigen in the absence of traditional APC to autologous MBP reactive T cell clones. MBP peptide-pulsed T cell clones specifically stimulated autologous MBP-reactive T cell clones to flux calcium and proliferate. Activation responses were peptide epitope specific and blocked by mAb to MHC class II, indicating a TCR-mediated response. In addition, mAb to the adhesion molecules LFA-3, CD2, LFA-1, CD29, and to the tyrosine phosphatase CD45 also inhibited proliferation, indicating the involvement of T to T cell interactions. In contrast to peptide Ag, T cell clones did not respond to autologous T cells pulsed with HPLC-purified MBP, suggesting that T cells are unable to process whole MBP. However, batch-purified MBP Ag preparations containing lower m.w. breakdown products were presented by T cells, indicating that naturally occurring breakdown products of autoantigens could be presented by activated T cells in vivo. These results raise the possibility that T cell presentation of autoantigen at inflammatory sites may be important in regulation of immune responses to self Ag.

Amino Acid Sequence↗
PubMed1990

Autoantibodies in the sera from newly diagnosed diabetic nod mice: evidence against cross-reactivity with a putative beta-cell surface autoantigen.

In insulin-dependent diabetes mellitus in humans, the BB rat and the NOD mouse, serum has been reported to contain autoantibodies that precipitate a 64,000 Mr protein from (32S) methionine labeled histoincompatible non-autoimmune rat or mouse islet cell proteins. Because experimental data reported recently have brought into question the role of the 64,000 Mr protein in targeting autoantibodies and hence initiate beta-cell destruction, we report differently designed experiments to clarify the apparent 64,000 Mr autoantigen enigma. Using an in vitro model of NOD mouse origin mimicking diabetic insulitis we found that target beta-cells induced a 6-fold increase in proliferative response of splenic L3T4+, Thy-1,2+ T cells. The magnitude of the proliferative response was not affected when target beta-cells were pretreated with 50% (vol/vol) partially purified immunoglobulins ((NH4)2SO4 precipitation at 33% saturation) from sera from newly diagnosed (less than 4d after onset) diabetic NOD mice. Cytofluorimetric analysis of beta-cells pretreated with partially purified immunoglobulins plus FITC-conjugated goat antimouse IgG as a second-step antibody were negative and thus gave no indication of an autoantigen-autoantibody complex formed on the surface of the beta-cells. We conclude from the experimental data that it remains still in question whether an autoantigen is targeted by an islet cell surface specific autoantibody and plays a role as a triggering event in the pathogenesis of diabetes in NOD mice.

Animals↗
PubMed1989

[Comparative studies on an autoantigen in ITP and the Baka alloantigen on platelet membrane glycoprotein IIb].

Platelet membrane glycoprotein (GP) IIb carries not only the Baka alloantigen but also an autoantigen in some patients with chronic idiopathic thrombocytopenic purpura (ITP). We previously reported one ITP patient (RY) with anti-GPIIb autoantibody in her plasma. In this report, we investigated whether the epitope of the autoantigen on GPIIb (case RY) is identical to that of the Baka alloantigen or not. The anti-Baka antibody used in this study was obtained from a mother with a child suffering from neonatal alloimmune thrombocytopenic purpura as reported by Okada et al. Immunoblotting showed that the anti-Baka antibody bound to GPIIb from Baka-positive platelets only. In contrast, the anti-GPIIb autoantibody in RY plasma bound to GPIIb, irrespective of Baka phenotype. In addition, after neuraminidase treatment of GPIIb on nitrocellulose paper, the anti-Baka antibody failed to bind to Baka-positive GPIIb, while the autoantibody still bound to GPIIb. From these data, we conclude that the epitope of the autoantigen in RY patient is different from that of the Baka alloantigen.

Antigen-Antibody Reactions↗
PubMed1988

Autoantigenic germ cells exist outside the blood testis barrier.

Preleptotene spermatocytes and spermatogonia are germ cells located outside the blood-testis barrier provided by the Sertoli cells. These cells have been found to express autoantigens accessible to circulating antibodies. Mice immunized with syngeneic testis with or without bacterial adjuvant had detectable IgG on cells at the periphery of seminiferous tubules. Sera from orchiectomized but not from testes-intact mice immunized with testis and adjuvants readily transferred similar IgG deposits to testes of normal recipients. When testis-specific antisera from orchiectomized mice and testis-intact mice were compared for their reactivity on prepuberal testicular cells, serum from orchiectomized donors had significantly higher reactivity. Ig was eluted from IgG-positive testes with acid buffer and was shown to be highly enriched in antibody to prepuberal testicular cells, confirming the Ag-specific nature of the IgG deposits. The testis IgG deposits reacted with antisera to IgG1 and IgG3 but not IgG2a or IgG2b. This finding can explain lack of association of C3 in the deposits. Only 30 to 40% of seminiferous tubules had IgG deposits and they coincided with stages 7 to 12 of the spermatogenic cycle. Thus, the expression of the autoantigens is stage specific. The in situ formation of immune complexes by circulating autoantibodies demonstrates conclusively that testis autoantigens are not completely sequestered, and the blood-testis barrier as an immunologic barrier is incomplete.

Aging↗
PubMed1984

Autoantibody to liver-specific lipoprotein in the mouse: regulation by naturally occurring autoantigen specific suppressor cells.

Indirect and direct evidence is presented that normal, non-immune mice have cells which suppress antibody production to murine liver specific lipoprotein (LSP) autoantigens with little or no effect on the response to a closely related foreign antigen complex, rabbit LSP. Suppressor control mechanisms were suggested in low responder BALB/c mice which produced LSP autoantibody only after exposure to low dose X-irradiation or treatment with cyclophosphamide. Adoptive transfer experiments in X-irradiated BALB/c mice and untreated C57BL/6 mice showed that cells from normal mouse spleen prevented LSP autoantibody production when put into the circulation of mice prior to immunization with foreign rabbit LSP. This suppressor activity was destroyed by treatment with antisera to T cells and by low dose X-irradiation. The normal spleen cells were ineffective as suppressors if given after primary immunization with rabbit LSP had commenced. It is suggested that the adoptive transfer of normal spleen cells prior to immunization with foreign LSP supplements homeostatic mechanisms in favour of tolerance to LSP autoantigen. It is argued that the LSP autoantibody response in the mouse is a unique model for the study of autoantigen specific naturally occurring suppression.

Animals↗
PubMed1995

The induction of renal autoantigen-specific T cells by a local Listeria monocytogenes infection.

In order to examine the possibility that a local chronic infection can induce organ-specific autoimmune disease, we inoculated unilateral kidneys with viable Listeria monocytogenes (intrarenal infection). The delayed footpad reaction against syngeneic kidney homogenate (KH) became positive from 1 week after initiating the intrarenal infection. A proliferative response of the spleen T cells from the infected mice was also observed against KH from 1 week after initiating the intrarenal infection, but no such response was seen against liver homogenate (LH). In contrast, an intravenous Listeria infection did not induce a delayed footpad reaction or proliferative response against KH, suggesting that these autoimmune responses were not caused by molecular mimicry between renal antigens and Listeria antigens. Furthermore, the ability to transfer the autoimmune response of spleen T cells from intrarenally infected mice was examined. The transferred mice showed a positive delayed footpad reaction against KH and an interstitial infiltration of mononuclear cells in their kidneys. These results demonstrate that the intrarenal Listeria infection induced renal autoantigen-specific T cells, which subsequently induced an autoimmune interstitial nephritis (AIN). The autoreactive T cells were all induced without immunization by autoantigens mixed with complete Freund's adjuvant. Based on these findings, we propose that a local bacterial infection may induce an autoimmune response against autoantigens in the infected organ and subsequently trigger organ-specific autoimmune disease.

Animals↗
PubMed1994

The 56K autoantigen is identical to human annexin XI.

Anti-56K autoantibodies are present in sera from patients with various autoimmune diseases, predominantly in sera from patients with rheumatoid arthritis, systemic lupus erythematosus, or Sjögren's syndrome. To clarify the molecular structure of this autoantigen, we isolated a 2.0-kilobase pair cDNA clone considered to encode the full-length 56K autoantigen. The longest open reading frame encodes a 505-amino acid polypeptide, with a predicted molecular mass of 54.4 kDa. The in vitro translated protein is recognized by all anti-56K positive patient sera tested. Antibodies affinity-purified using the bacterially expressed recombinant protein recognized the 56K autoantigen in a HeLa cell extract. cDNA sequencing revealed that the 56K cDNA shares a high degree of homology in both nucleotide (87%) and amino acid sequence (92.5%) with bovine annexin XI, indicating that the 56K cDNA encodes the human homologue of annexin XI, a member of the Ca(2+)-dependent phospholipid binding protein family. Anti-56K autoantibody exhibits both a cytoplasmic and a nuclear staining in immunofluorescence experiments. Patients' sera recognize preferentially the N-terminal region of the protein, which is specific for 56K/annexin XI and not shared by other annexins, indicating that the autoimmune response to 56K/annexin XI in these patients is specific for this annexin family member.

Amino Acid Sequence↗
PubMed1993

Autoantigenic epitopes of the B and D polypeptides of the U1 snRNP. Analysis of domains recognized by the Y12 monoclonal anti-Sm antibody and by patient sera.

Anti-Sm antibodies, a specific marker for SLE, are directed against the B'/B and D polypeptides of Sm small nuclear ribonucleoproteins. The Y12 monoclonal anti-Sm antibody (Y12 mAb), as well as many anti-Sm patient sera, recognize cross-reactive epitopes on the B'/B and D polypeptides. This immunoreactive site is of special interest since polypeptides B and D share little amino acid sequence homology. In the present study, we have sought to establish the autoantigenic domain of polypeptides B and D that accounts for this epitope. We tested the ability of the Y12 mAb and anti-Sm sera to immunoprecipitate truncated forms of polypeptides B and D translated in vitro from mRNA bearing 5' and 3' end deletions. Most anti-Sm sera bound epitopes at the carboxyl-terminus of polypeptide B, however, autoantigenic epitopes were also found at the amino-terminus (amino acids 1 to 83 and 104 to 115). Surprisingly, the Y12 mAb recognized nonoverlapping amino-terminal and carboxyl-terminal halves of polypeptide B. One putative Y12 mAb binding site (amino acids 104 to 115) indicated by carboxyl-terminal deletion studies was confirmed through recognition of a corresponding synthetic peptide. Deletion studies with polypeptide D demonstrated a major autoantigenic domain on the carboxyl-terminus (amino acids 85 to 119) that was necessary for recognition by the Y12 mAb and by 7/14 patient sera. These results indicate that a cross-reactive epitope on B'/B and D, as defined by the Y12 mAb, resides on at least two different domains of polypeptide B and localizes to the carboxyl-terminus of polypeptide D. From the shared homology of truncated forms of B and D polypeptides recognizable with the Y12 mAb, we suspect that some form of GRG motif is involved in developing the Y12 mAb epitope that may involve other residues and be largely conformational in nature.

Amino Acid Sequence↗