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PubMed1989

MHC-restricted autoantigen-reactive T cell clones in multiple sclerosis.

Multiple sclerosis is a demyelinating disease of the central nervous system with genetic, viral and autoimmune characteristics. Myelin basic protein (MBP) is a suspected target autoantigen since it induces experimental autoimmune encephalomyelitis, an animal model closely resembling multiple sclerosis. The disease is mediated by Class II restricted, MBP-reactive T cells possessing the T helper/inducer phenotype. In the present study, we have isolated MBP-reactive T cell clones from the peripheral blood of a chronic progressive multiple sclerosis patient. The clones displayed blastogenic memory responses when rechallenged with the autoantigen and irradiated autologous lymphocytes. MBP recognition by the autoantigen-reactive T lymphocytes was restricted by major histocompatibility complex Class II antigens. Both CD4+8- and CD4-8+ MBP-reactive T cell clones were obtained.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1994

La autoantigen alleviates translational repression by the 5' leader sequence of the human immunodeficiency virus type 1 mRNA.

The trans-activation response element (TAR) at the 5' end of the human immunodeficiency virus type 1 (HIV-1) mRNAs forms a stable hairpin structure which is a target for binding of the virally encoded protein Tat, which activates viral gene expression, as well as several cellular factors. TAR is also inhibitory to translation. One of several host factors that binds to TAR RNA is the La autoantigen, an RNA-binding protein which functions in RNA polymerase III transcription termination and has also been implicated in cap-independent internal translation initiation on poliovirus RNA. Here we show that La autoantigen alleviates translational repression by the HIV-1 leader RNA. In rabbit reticulocyte lysate, La relieves the cis-inhibitory effect of the TAR RNA on translation of bacterial chloramphenicol acetyltransferase (CAT) mRNA but not inhibition that is mediated by an artificial secondary structure element. Canonical translation factors exhibited slight (eIF-2 and GEF) or no (eIF-4A, eIF-4B, eIF-4E, eIF-4F, eIF-3, and eEF-1 alpha) stimulatory activity on translation of TAR-containing CAT mRNA. In addition, we show that poliovirus RNA, in spite of being an inefficient template in rabbit reticulocyte lysate, is a strong competitive inhibitor of translation of TAR-containing CAT mRNA but not CAT mRNA. This inhibition can be relieved by La but not by any other translation factor. The results suggest a possible involvement of the La autoantigen in HIV-1 gene expression.

Autoantigens↗
PubMed1994

Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens.

Oral tolerance is a long recognized method to induce peripheral immune tolerance. The primary mechanisms by which orally administered antigen induces tolerance are via the generation of active suppression or clonal anergy. Low doses of orally administered antigen favor active suppression whereas higher doses favor clonal anergy. The regulatory cells that mediate active suppression act via the secretion of suppressive cytokines such as TGF beta and IL-4 after being triggered by the oral tolerogen. Furthermore, antigen that stimulates the gut-associated lymphoid tissue preferentially generates a Th2 type response. Because the regulatory cells generated following oral tolerization are triggered in an antigen-specific fashion but suppress in an antigen nonspecific fashion, they mediate "bystander suppression" when they encounter the fed autoantigen at the target organ. Thus it may not be necessary to identify the target autoantigen to suppress an organ-specific autoimmune disease via oral tolerance; it is necessary only to administer orally a protein capable of inducing regulatory cells that secrete suppressive cytokines. Orally administered autoantigens suppress several experimental autoimmune models in a disease- and antigen-specific fashion; the diseases include experimental autoimmune encephalomyelitis (EAE), uveitis, and myasthenia, collagen- and adjuvant-induced arthritis, and diabetes in the NOD mouse. In addition, orally administered alloantigen suppresses alloreactivity and prolongs graft survival. Initial clinical trials of oral tolerance in multiple sclerosis, rheumatoid arthritis, and uveitis have demonstrated positive clinical effects with no apparent toxicity and decreases in T cell autoreactivity.

Administration, Oral↗
PubMedDate not supplied

Dithranol and dimethylfumarate suppress the interferon-gamma-induced up-regulation of cytokeratin 17 as a putative psoriasis autoantigen in vitro.

In psoriasis an etiopathogenetic vicious circle has been hypothesized in which disease manifestation is triggered by skin-specific autoantigen structures. Autoreactive T cells are supposed to mediate inflammation and hyperproliferation in the epidermopapillary compartment, positively feeding back the expression and accessibility of decisive antigen structures. Recently an epitope within cytokeratin 17 (K17) has been described as such a putative psoriasis autoantigen, which is moreover known to be up-regulated under the influence of proinflammatory interferon-gamma (IFN-gamma), which is abundantly detected in psoriatic plaques. The present study proposes an in vitro model for this presumptive IFN-gamma/K17 autoimmune loop, i.e. the incubation of hyperproliferative human HaCaT keratinocytes with 25 U IFN-gamma/ml for 72 h. This treatment led to a significant up-regulation of K17 protein expression (> or =300%) measured by flow immunocytometry as compared to the untreated control (100%, p < or = 0.05). Preincubation with a subcytotoxic and antiproliferative dithranol concentration as low as 0.3 microM for 2 h prior to the IFN-gamma exposure resulted in a K17 expression that was significantly lower than the IFN-gamma-induced K17 expression reference level. The IFN-gamma-induced K17 expression was also significantly lowered by coincubation with a subcytotoxic and nonantiproliferative concentration of 3 microM dimethylfumarate. The data indicate for dithranol and dimethylfumarate that a part of their antipsoriatic mode of action may be related to a direct down-regulation of putative psoriasis autoantigen structures.

Administration, Topical↗
PubMed1992

Serological cross-reactivity between a human Ro/SS-A autoantigen (calreticulin) and the lambda Ral-1 antigen of Onchocerca volvulus.

We have cloned and sequenced a 46-kD Ro/SS-A autoantigen gene that is the human homologue of the calcium-binding protein, calreticulin. The sequence of this 46-kD Ro/SS-A protein (calreticulin) has significant homology to lambda Ral-1, a recombinant cDNA clone corresponding to a major antigen of the nematode, Onchocerca volvulus, the infectious agent of onchocerciasis. We therefore sought to determine whether antibodies produced by onchocerciasis patients might crossreact with the human 46-kD Ro/SS-A autoantigen (calreticulin). 20 of 22 sera from Liberian onchocerciasis patients who had no known evidence of autoimmune disease were found to contain antibodies that reacted with the 46-kD Ro/SS-A (calreticulin) by immunoblot analysis. Characteristic of sera reactive with Ro/SS-A antigens, some onchocerciasis sera also immunoprecipitated the Ro/SS-A-associated hY RNAs. In addition, a monoclonal antibody raised against O. volvulus organisms reacted to purified human WiL-2 cell 46 kD Ro/SS-A antigen (calreticulin) by ELISA. These results strongly suggest that onchocerciasis patients produce antibodies that crossreact with the 46-kD human Ro/SS-A autoantigen (calreticulin) and raise the possibility that infectious organisms such as O. volvulus might play a triggering or exacerbating role in the human Ro/SS-A autoimmune response.

Amino Acid Sequence↗
PubMed2002

Interleukin-10-mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen.

Regulatory T cells have been shown to control animal models of immune-mediated pathology by inhibitory cytokine production, but little is known about such cells in human disease. Here we characterize regulatory T-cell responses specific for a human red blood cell autoantigen in patients with warm-type autoimmune hemolytic anemia. Peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia were found either to proliferate and produce interferon-gamma or to secrete the regulatory cytokine interleukin 10 when stimulated in vitro with a major red blood cell autoantigen, the RhD protein. Flow cytometric analysis confirmed that the majority of the responding cells were of the CD4(+) phenotype. Serial results from individual patients demonstrated that this bias toward proliferative or interleukin-10 responses was unstable over time and could reverse in subsequent samples. Epitope mapping studies identified peptides from the sequence of the autoantigen that preferentially induced interleukin-10 production, rather than proliferation, and demonstrated that many contain naturally processed epitopes. Responses to such peptides suppressed T-cell proliferation against the RhD protein, an inhibition that was mediated largely by interleukin 10 and dependent on cytotonic T lymphocyte-associated antigen (CTLA-4) costimulation. Antigenic peptides with the ability to stimulate specific regulatory cells may represent a new class of therapeutic agents for immune-mediated disease.

Abatacept↗
PubMed2005

Screening of an endothelial cDNA library identifies the C-terminal region of Nedd5 as a novel autoantigen in systemic lupus erythematosus with psychiatric manifestations.

Anti-endothelial-cell antibodies are associated with psychiatric manifestations in systemic lupus erythematosus (SLE). Our primary aim in this study was to seek and characterize molecules that behave as endothelial autoantigens in SLE patients with psychiatric manifestations. By screening a cDNA library from human umbilical artery endothelial cells with serum from an SLE patient with psychosis, we identified one positive strongly reactive clone encoding the C-terminal region (C-ter) of Nedd5, an intracytoplasmatic protein of the septin family. To evaluate anti-Nedd5 serum immunoreactivity, we analyzed by ELISA specific IgG responses in 17 patients with SLE and psychiatric manifestations (group A), 34 patients with SLE without psychiatric manifestations (group B), 20 patients with systemic sclerosis, 20 patients with infectious mononucleosis, and 35 healthy subjects. IgG specific to Nedd5 C-ter was present in 14 (27%) of the 51 SLE patients. The mean optical density value for IgG immunoreactivity to Nedd5 C-ter was significantly higher in patients of group A than in those of group B, those with infectious mononucleosis, or healthy subjects (0.17 +/- 0.14 vs, respectively, 0.11 +/- 0.07, P = 0.04; 0.11 +/- 0.06, P = 0.034; and 0.09 +/- 0.045, P = 0.003, on Student's t-test). Moreover, IgG immunoreactivity to Nedd5 C-ter was significantly higher in patients with systemic sclerosis than in patients of group B or healthy subjects (0.18 +/- 0.18 vs, respectively, 0.11 +/- 0.07, P = 0.046; and 0.09 +/- 0.045, P = 0.003). The percentage of patients with anti-Nedd5 C-ter serum IgG was higher in group A than in group B (8 (47%) of 17, vs 6 (17%) of 34, P = 0.045, on Fisher's exact test). In order to clarify a possible mechanism by which Nedd5 might be autoantigenic, we observed that Nedd5 relocated from cytoplasm to the plasma membrane of EAhy926 endothelial cells after apoptotic stimuli. In conclusion, Nedd5 is a novel autoantigen of potential clinical importance that could be successfully used for a more thorough investigation of the pathogenesis of psychiatric manifestations in SLE. Although anti-Nedd5 autoantibodies are not specific to SLE, they are significantly associated with neuropsychiatric SLE and may represent immunological markers of psychiatric manifestations in this pathology.

Adult↗
PubMed2005

Identification of kinectin as a novel Behçet's disease autoantigen.

There has been some evidence that Behçet's disease (BD) has a significant autoimmune component but the molecular identity of putative autoantigens has not been well characterized. In the initial analysis of the autoantibody profile in 39 Chinese BD patients, autoantibodies to cellular proteins were uncovered in 23% as determined by immunoblotting. We have now identified one of the major autoantibody specificities using expression cloning. Serum from a BD patient was used as a probe to immunoscreen a lambdaZAP expression cDNA library. Candidate autoantigen cDNAs were characterized by direct nucleotide sequencing and their expressed products were examined for reactivity to the entire panel of BD sera using immunoprecipitation. Reactivity was also examined with normal control sera and disease control sera from patients with lupus and Sjögren's syndrome. Six independent candidate clones were isolated from the cDNA library screen and were identified as overlapping partial human kinectin cDNAs. The finding that kinectin was an autoantigen was verified in 9 out of 39 (23%) BD patient sera by immunoprecipitation of the in vitro translation products. Sera from controls showed no reactivity. The significance of kinectin as a participant in autoimmune pathogenesis in BD and the potential use of autoantibody to kinectin in serodiagnostics are discussed.

Adult↗
PubMed1995

Identification of the main gonadal autoantigens in patients with adrenal insufficiency and associated ovarian failure.

Autoimmune adrenal insufficiency is associated with premature ovarian failure at frequencies of 10-20%. In these patients a reactivity against an unknown steroid cell antigen in both the adrenal glands and gonads has been described. We have recently identified the cytochrome P450 enzyme 21-hydroxylase and the side-chain cleavage enzyme (SCC) as the major adrenal autoantigens in Addison's disease and the rare autoimmune polyendocrine syndrome type I (APS-I), respectively. In an attempt to identify the steroid cell antigen, sera from patients with Addison's disease (n = 13) and APS-I (n = 7) that reacted with Leydig cells were selected. Preparations of isolated human granulosa cells, isolated rat Leydig cells, and fractions of human placenta were used in Western blots. All sera were also tested against bacterially expressed 21-hydroxylase, SCC, and 17 alpha-hydroxylase. The SCC was recognized by sera from patients with Addison's disease and those with APS-I. In addition, a majority of the sera (n = 12) reacted with a novel 51-kilodalton autoantigen present in granulosa cells and placenta. The results show that the steroid cell autoantigen consists mainly of the SCC and a novel protein of unknown function.

Addison Disease↗
PubMed2002

Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as alpha-enolase.

Lymphocytic hypophysitis is part of the spectrum of organ-specific autoimmune diseases, and although its histopathology is well documented, its pathogenesis is unclear. Serum autoantibodies directed against a 49-kDa cytosolic protein are detected by immunoblotting in 70% of patients with biopsy-proven lymphocytic hypophysitis. Here we report the purification and identification of this first target autoantigen in lymphocytic hypophysitis. The autoantigen has a molecular mass of 49 kDa, a cytosolic localization, and a ubiquitous tissue distribution. The 49-kDa protein was purified from monkey brain and human placental cytosol. Limited amino acid sequencing after proteolytic digestion of the human placental protein showed identity with alpha-enolase. The identification was confirmed using sera from patients with pituitary autoimmunity, which strongly reacted with recombinant human alpha-enolase and yeast enolase, but not with rabbit muscle beta- enolase. This indicates that the immunoreactive epitopes are largely conserved from yeast to human, but are not present in beta-enolase. alpha-Enolase autoantibodies are not specific to pituitary autoimmune disease and have been reported in other autoimmune diseases. However, this study is the first to indicate a role for alpha-enolase as an autoantigen in lymphocytic hypophysitis.

Amino Acid Sequence↗
PubMed2005

Autoantigenic epitopes on platelet glycoproteins.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by early platelet destruction mediated by antiplatelet autoantibodies. Platelet membrane glycoproteins (GP), especially GPIIb-IIIa and GPIb-IX, contain major autoantigenic determinants in chronic ITP. Recent advances in the localization of autoantigens as well as in the detection of GP-specific antibodies have improved our understanding of the pathophysiology of the disease. The N-terminal globular head of GPIIb-IIIa, particularly the beta-propeller domain in GPIIb, seems to play an important role as a hot spot for autoantigenic epitopes in chronic ITP.

Autoantibodies↗
PubMed1996

Beta-cell markers and autoantigen expression by a human insulinoma cell line: similarities to native beta cells.

In the present study we have evaluated the expression of different beta-cell markers, islet molecules and auto-antigens relevant in diabetes autoimmunity by a human insulinoma cell line (CM) in order to define its similarities with native beta cells and to discover whether it could be considered as a model for studies on immunological aspects of Type 1 diabetes. First, the positivity of the CM cell line for known markers of neuroendocrine derivation was determined by means of immunocytochemical analysis using different anti-islet monoclonal antibodies including A2B5 and 3G5 reacting with islet gangliosides, and HISL19 binding to an islet glycoprotein. Secondly, the expression and characteristics of glutamic acid decarboxylase (GAD) and of GM2-1 ganglioside, both known to be islet autoantigens in diabetes autoimmunity and expressed by human native beta cells, were investigated in the CM cell line. The pattern of ganglioside expression in comparison to that of native beta cells was also evaluated. Thirdly, the binding of diabetic sera to CM cells reacting with islet cytoplasmic antigens (ICA) was studied by immunohistochemistry. The results of this study showed that beta cell markers identified by anti-islet monoclonal antibodies A2B5, 3G5 and HISL-19 are expressed by CM cells; similarly, islet molecules such as GAD and GM2-1 ganglioside are present and possess similar characteristics to those found in native beta cells; the pattern of expression of other gangliosides by CM cells is also identical to human pancreatic islets; beta cell autoantigen(s) reacting with antibodies present in islet cell antibodies (ICA) positive diabetic sera identified by ICA binding are also detectable in this insulinoma cell line. We conclude that CM cells show close similarities to native beta cells with respect to the expression of neuro-endocrine markers, relevant beta cell autoantigens in Type 1 diabetes (GAD, GM2-1, ICA antigen), and other gangliosides. Therefore, this insulinoma cell line may be considered as an ideal model for studies aimed at investigating autoimmune phenomena occurring in Type 1 diabetes.

Autoantigens↗
PubMed1996

Characterization of human DNA topoisomerase II as an autoantigen recognized by patients with IDDM.

Autoantibodies against several cytoplasmic autoantigens such as glutamic acid decarboxylase, heat shock protein 65, insulin, and carboxypeptidase H have been identified in the sera of patients with IDDM. To investigate whether type II DNA topoisomerase (TopII) is an autoantigen in IDDM patients, we have constructed a series of overlapping DNA TopII fragments that covered the entire length of this enzyme. These fragments were used as antigens to screen sera of IDDM patients. We have examined 195 Chinese IDDM patients (mean age 14.2 +/- 7.5 years, age at onset 9.2 +/- 6.4 years, duration of diabetes 4.6 +/- 3.4 years) and 51 nondiabetic individuals. The results showed that DNA TopII autoantibodies were detected in 49.2 and 47.2% of IDDM patients using purified TopII fragments and full-length TopII as antigens, respectively. The frequency of anti-TopII positivity was relatively stable irrespective of sex and disease duration. The patients were slightly older at onset and the prevalence of anti-thyroglobulin/anti-microsomal autoantibodies was twice that in the IDDM subgroup positive for anti-TopII than in IDDM patients who were negative for anti-TopII. We also characterized the epitopes of DNA TopII that were recognized by IDDM sera. Those epitopes resided mostly in three distinct domains. One resided in amino acid residues 1-147, another in amino acid residues 286-472, and the third in the COOH-terminal one-third of DNA TopII. Intriguingly, we found that these epitopes shared similarity (up to 36% identity and 63.6% homology) to previously identified epitopes of IDDM autoantigens.

Adolescent↗
PubMed1996

T-cell responses to autoantigens in IDDM. The search for the Holy Grail.

IDDM (type I diabetes) is generally believed to result from T-cell-mediated autoimmune destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans. In the last few years, considerable progress has been made with regard to the identification and characterization of candidate autoantigens recognized by autoantibodies; several of these candidate autoantigens are recognized by T-cells, including insulin, GAD65 and GAD67, heat-shock protein 65 (hsp65), and islet-cell antigen 69 (ICA69). In addition to these, a number of unidentified beta-cell antigens, including insulin-secretory granule membrane proteins and a 38-kDa protein, have been shown to stimulate T-cells of IDDM patients. However, T-cell autoreactivity to islet antigens is not specific for IDDM, and the T-cell target antigens are not specific for beta-cells. Moreover, the autoantigens involved in the initiation of the insulitis must be defined, and the mechanism of the T-cell-dependent beta-cell destruction remains to be unraveled. This review focuses on T-cell autoreactivity in IDDM in humans and the implications of the present knowledge for immunointervention and monitoring of immunotherapeutic trials.

Animals↗
PubMed2004

T-cell receptor transgenic response to an endogenous polymorphic autoantigen determines susceptibility to diabetes.

We have produced a T-cell receptor (TCR) transgenic NOD mouse, 6.9TCR/NOD, in which the expression of both diabetogenic T-cells and naturally occurring autoantigen were simultaneously controlled. The parent T-cell clone, BDC-6.9, and T-cells from 6.9TCR/NOD mice recognize a currently unidentified antigen present in NOD but not in BALB/c islet cells. A gene that codes for the antigen, or a protein that regulates the antigen, was previously mapped to a locus on chromosome 6. We have developed transgenic mice bearing the TCR alpha- and beta-chains from the BDC-6.9 T-cell clone on a NOD congenic background in which the antigen locus on chromosome 6 of the NOD mouse is replaced by a segment from BALB/c. These NOD.C6 congenic mice lack the NOD islet cell antigen to which the BDC-6.9 T-cell clone responds. Diabetes in both male and female 6.9TCR/NOD mice is dramatically accelerated, but in 6.9TCR/NOD.C6 mice lacking the NOD islet cell autoantigen, we have not observed diabetes for up to 1 year of age. Thus, the generation of 6.9TCR transgenic mice provides a model of autoimmune diabetes whereby controlled expression of an endogenous polymorphic autoantigen effectively determines disease development.

Animals↗
PubMed2004

HLA-DQ-regulated T-cell responses to islet cell autoantigens insulin and GAD65.

HLA-DQ is strongly associated with genetic predisposition to type 1 diabetes. It is assumed that HLA-DQ molecules exert their effects on the disease via the presentation of peptides from islet autoantigens to CD4(+) T-cells, but little information regarding HLA-DQ-restricted, islet antigen-specific, autoreactive T-cells is available. To investigate the role of HLA-DQ in the immune response to islet autoantigens, we measured T-cell proliferation to insulin and GAD65 in the presence and absence of monoclonal antibodies that block HLA-DQ-mediated antigen presentation in recent-onset type 1 diabetic patients and their siblings. Positive proliferative T-cell responses to GAD65 were observed in 60% of type 1 diabetic patients and 52% of siblings. This proliferation was significantly reduced in the presence of anti-DQ antibody, demonstrating the presence of primed, effector HLA-DQ-restricted T-cell responses to GAD65. Positive proliferative responses to insulin were observed in 25% of type 1 diabetic patients and 10% of siblings. However, blocking HLA-DQ-restricted T-cell responses led to a significant increase in proliferation to insulin, implying the presence of primed suppressive HLA-DQ-restricted T-cell responses to insulin. These results indicate that HLA-DQ acts as a restriction element for both proliferative and suppressor cells, with the relative balance of these cells dependent on the nature of the autoantigen.

Alleles↗
PubMed1994

Human gastric H,K-adenosine triphosphatase beta-subunit is a major autoantigen in atrophic corpus gastritis. Expression of the recombinant human glycoprotein in insect cells.

BACKGROUND: Sera from patients with atrophic corpus gastritis with pernicious anemia frequently contain parietal cell autoantibodies. We have previously demonstrated that the human H,K-adenosine triphosphatase (H,K-ATPase) alpha-subunit constitutes a major autoantigen. The present study investigates whether the human H,K-ATPase beta-subunit is an autoantigen, too, METHODS: The gene of the human beta-subunit was expressed in insect cells by a baculovirus expression system. The reactivity of sera from 42 patients towards the recombinant glycoprotein was analyzed by means of an enzyme-linked immunosorbent assay. RESULTS: Thirty-nine of the 42 sera (93%) scored positive. Autoantibody binding in 41 sera (98%) was eliminated when unglycosylated beta-subunit was used as antigen, and antibody binding in the last serum was decreased by 30%. CONCLUSIONS: The results indicate that the beta-subunit is indeed a major autoantigen and that carbohydrates are involved in binding of the autoantibodies.

Adult↗
PubMedDate not supplied

Hepatic and biliary autoantigens.

Chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC) are two enigmatic liver diseases in which autoimmunity is implicated. Provisional criteria to separate the autoimmune type of CAH (A-CAH) from others are specified. Western immunoblotting using disease sera and antibody screening of a rat liver gene expression library were used to identify hepatic and biliary autoantigens relevant to the pathogenesis of A-CAH or PBC. With all reported putative liver-specific autoantigen preparations, serum reactivity in A-CAH and CAH due to infection with hepatitis B virus tends to be similar. In A-CAH, immunoblotting showed multiple reactivities with all liver preparations used, including hepatocyte membrane. In PBC, immunoblotting showed two disease-specific polypeptide antigens of MW 70 and 45 kD. A cDNA clone derived from a rat liver gene expression library was shown to encode the antigenic site of the 70 kD polypeptide. Recently published work in two other laboratories has established that the 70 kD autoantigen is the E2 component of the pyruvate dehydrogenase enzyme (PDH), and a proposed antibody-binding site (autoepitope) is a conserved decapeptide, corresponding to residues 83-92 of the deduced amino acid sequence of M2, which is the binding site of lipoic acid to the E2 component of PDH.

Autoantigens↗