{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T22:06:00Z","timestamp":1758405960301},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2004,12,11]],"date-time":"2004-12-11T00:00:00Z","timestamp":1102723200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2004,12,11]],"date-time":"2004-12-11T00:00:00Z","timestamp":1102723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Walking along disease-associated protein sequences in the search for specific segments able to induce cellular immune response may direct clinical research towards effective peptide-based vaccines. To this aim, we are studying the targets of the immune response in autoimmune diseases by applying the principle of non-self-discrimination as a driving concept in the identification of the autoimmunogenic peptide sequences.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Computer-assisted proteomic analysis of the autoantigen protein sequence and dot-blot\/NMR immunoassays are applied to the prediction and subsequent validation of the epitopic sequences.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Using the experimental model <jats:italic>Pemphigus vulgaris<\/jats:italic>\/desmoglein 3, we have identified the antigenic linear determinant recognized by MAb 5H10, a monoclonal antibody raised against the extracellular domain of human desmoglein-3. The computer-assisted search for the Dsg3 epitope was conducted by analyzing the similarity level to the mouse proteome of the human desmoglein protein sequence. Dot-blot immunoassay analyses mapped the epitope within the sequence Dsg3<jats:sub>49\u201360<\/jats:sub> REWVKFAKPCRE, which shows low similarity to the mouse proteome. NMR spectroscopy analyses confirmed the specificity of MAb 5H10 for the predicted epitope.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>This report promotes the concept that low level of sequence similarity to the host's proteome may modulate peptide epitopicity.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1479-5876-2-43","type":"journal-article","created":{"date-parts":[[2005,1,12]],"date-time":"2005-01-12T16:05:43Z","timestamp":1105545943000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Epitope definition by proteomic similarity analysis: identification of the linear determinant of the anti-Dsg3 MAb 5H10"],"prefix":"10.1186","volume":"2","author":[{"given":"Alberta","family":"Lucchese","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham","family":"Mittelman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mong-Shang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darja","family":"Kanduc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Animesh A","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2004,12,11]]},"reference":[{"key":"57_CR1","doi-asserted-by":"publisher","first-page":"8368","DOI":"10.1073\/pnas.92.18.8368","volume":"92","author":"JL Cornette","year":"1995","unstructured":"Cornette JL, Margalit H, Berzofsky JA, DeLisi C: Periodic variation in side-chain polarities of T-cell antigenic peptides correlates with their structure and activity. Proc Natl Acad Sci USA. 1995, 92: 8368-8372.","journal-title":"Proc Natl Acad Sci USA"},{"key":"57_CR2","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/0264-410X(94)00014-E","volume":"13","author":"GE Meister","year":"1995","unstructured":"Meister GE, Roberts CGP, Berzofsky JA, De Groot AS: Two novel T cell epitope prediction algorithms based on MHC-binding motifs; comparison of predicted and published epitopes from Mycobacterium tuberculosis and HIV protein sequences. Vaccine. 1995, 13: 581-591. 10.1016\/0264-410X(94)00014-E.","journal-title":"Vaccine"},{"key":"57_CR3","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s002510050595","volume":"50","author":"H Rammensee","year":"1999","unstructured":"Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S: SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999, 50: 213-219. 10.1007\/s002510050595.","journal-title":"Immunogenetics"},{"key":"57_CR4","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1093\/bioinformatics\/16.3.290","volume":"16","author":"PB McGarvey","year":"2000","unstructured":"McGarvey PB, Huang H, Barker WC, Orcutt BC, Garavelli JS, Srinivasarao GY, Yeh LS, Xiao C, Wu CH: PIR: a new resource for bioinformatics. Bioinformatics. 2000, 16: 290-291. 10.1093\/bioinformatics\/16.3.290.","journal-title":"Bioinformatics"},{"key":"57_CR5","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1006\/jmbi.2000.3683","volume":"298","author":"C Kuttler","year":"2000","unstructured":"Kuttler C, Nussbaum AK, Dick TP, Rammensee HG, Schild H, Hadeler KP: An algorithm for the prediction of proteasomal cleavages. J Mol Biol. 2000, 298: 417-429. 10.1006\/jmbi.2000.3683.","journal-title":"J Mol Biol"},{"key":"57_CR6","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/35105075","volume":"1","author":"JA Berzofsky","year":"2001","unstructured":"Berzofsky JA, Ahlers JD, Belyakov IM: Strategies for designing and optimizing new generation vaccines. Nat Rev Immunol. 2001, 1: 209-219. 10.1038\/35105075.","journal-title":"Nat Rev Immunol"},{"key":"57_CR7","doi-asserted-by":"publisher","first-page":"9952","DOI":"10.1073\/pnas.1633254100","volume":"100","author":"DL Doolan","year":"2003","unstructured":"Doolan DL, Southwood S, Freilich DA, Sidney J, Graber NL, Shatney L, Bebris L, Florens L, Dobano C, Witney AA, Appella E, Hoffman SL, Yates JR, Carucci DJ, Sette A: Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data. Proc Natl Acad Sci USA. 2003, 100: 9952-9957. 10.1073\/pnas.1633254100.","journal-title":"Proc Natl Acad Sci USA"},{"key":"57_CR8","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/S0196-9781(99)00095-9","volume":"20","author":"J Willers","year":"1999","unstructured":"Willers J, Lucchese A, Kanduc D, Ferrone S: Molecular mimicry of phage displayed peptides mimicking GD3 ganglioside. Peptides. 1999, 20: 1021-1026. 10.1016\/S0196-9781(99)00095-9.","journal-title":"Peptides"},{"key":"57_CR9","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1046\/j.1440-1711.2000.00949.x","volume":"78","author":"C Natale","year":"2000","unstructured":"Natale C, Giannini T, Lucchese A, Kanduc D: Computer-assisted analysis of molecular mimicry between HPV16 E7 oncoprotein and human protein sequences. Immunol Cell Biol. 2000, 78: 580-585. 10.1046\/j.1440-1711.2000.00949.x.","journal-title":"Immunol Cell Biol"},{"key":"57_CR10","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1002\/ijc.10259","volume":"98","author":"A Mittelman","year":"2002","unstructured":"Mittelman A, Lucchese A, Sinha AA, Kanduc D: Monoclonal and polyclonal humoral immune response to EC HER-2\/NEU peptides with low similarity to the host's proteome. Int J Cancer. 2002, 98: 741-747. 10.1002\/ijc.10259.","journal-title":"Int J Cancer"},{"key":"57_CR11","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1111\/j.0022-202X.2004.23417.x","volume":"123","author":"A Mittelman","year":"2004","unstructured":"Mittelman A, Tiwari R, Lucchese G, Willers J, Dummer R, Kanduc D: Identification of Monoclonal Anti-HMW-MAA Antibody Linear Peptide Epitope by Proteomic Database Mining. J Invest Dermat. 2004, 123: 670-675. 10.1111\/j.0022-202X.2004.23417.x.","journal-title":"J Invest Dermat"},{"key":"57_CR12","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1002\/ijc.20310","volume":"111","author":"R Dummer","year":"2004","unstructured":"Dummer R, Mittelman A, Fanizzi FP, Lucchese G, Willers J, Kanduc D: Non-self-discrimination as a driving concept in the identification of an immunodominant HMW-MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients. Int J Cancer. 2004, 111: 720-726. 10.1002\/ijc.20310.","journal-title":"Int J Cancer"},{"key":"57_CR13","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/0470871628.ch12","volume":"252","author":"E Sercarz","year":"2003","unstructured":"Sercarz E, Maverakis E, van den Elzen P, Madakamutil L, Kumar V: Seven surprises in the TCR-centred regulation of immune responsiveness in an autoimmune system. Novartis Found Symp. 2003, 252: 165-171.","journal-title":"Novartis Found Symp"},{"key":"57_CR14","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1083\/jcb.122.2.409","volume":"122","author":"S Karpati","year":"1993","unstructured":"Karpati S, Amagai M, Prussick R, Cehrs K, Stanley JR: Pemphigus vulgaris antigen, a desmoglein type of cadherin, is localized within keratinocyte desmosomes. J Cell Biol. 1993, 122: 409-415. 10.1083\/jcb.122.2.409.","journal-title":"J Cell Biol"},{"key":"57_CR15","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/1523-1747.ep12316680","volume":"105","author":"AP Kowalczyk","year":"1995","unstructured":"Kowalczyk AP, Anderson JE, Borgwardt JE, Hashimoto T, Stanley JR, Green KJ: Pemphigus sera recognize conformationally sensitive epitopes in the amino-terminal region of desmoglein-1. J Invest Dermatol. 1995, 105: 147-152. 10.1111\/1523-1747.ep12316680.","journal-title":"J Invest Dermatol"},{"key":"57_CR16","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/S0190-9622(03)02160-1","volume":"49","author":"Y Futei","year":"2003","unstructured":"Futei Y, Amagai M, Hashimoto T, Nishikawa T: Conformational epitope mapping and IgG subclass distribution of desmoglein 3 in paraneoplastic pemphigus. J Am Acad Dermatol. 2003, 49: 1023-1028. 10.1016\/S0190-9622(03)02160-1.","journal-title":"J Am Acad Dermatol"},{"key":"57_CR17","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.4049\/jimmunol.170.4.2170","volume":"170","author":"K Tsunoda","year":"2003","unstructured":"Tsunoda K, Ota T, Aoki M, Yamada T, Nagai T, Nakagawa T, Koyasu S, Nishikawa T, Amagai M: Induction of pemphigus phenotype by a mouse monoclonal antibody against the amino-terminal adhesive interface of desmoglein 3. J Immunol. 2003, 170: 2170-2178.","journal-title":"J Immunol"},{"key":"57_CR18","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.jdermsci.2004.03.011","volume":"35","author":"H Anzai","year":"2004","unstructured":"Anzai H, Fujii Y, Nishifuji K, Aoki-Ota M, Ota T, Amagai M, Nishikawa T: Conformational epitope mapping of antibodies against desmoglein 3 inexperimental murine pemphigus vulgaris. J Dermatol Sci. 2004, 35: 133-142. 10.1016\/j.jdermsci.2004.03.011.","journal-title":"J Dermatol Sci"},{"key":"57_CR19","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1046\/j.1523-1747.1998.00086.x","volume":"110","author":"M Hertl","year":"1998","unstructured":"Hertl M, Amagai M, Sundaram H, Stanley J, Ishii K, Katz SI: Recognition of desmoglein 3 by autoreactive T cells in pemphigus vulgaris patients and normals. J Invest Dermatol. 1998, 110: 62-66. 10.1046\/j.1523-1747.1998.00086.x.","journal-title":"J Invest Dermatol"},{"key":"57_CR20","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1172\/JCI10305","volume":"106","author":"VT Nguyen","year":"2000","unstructured":"Nguyen VT, Ndoye A, Shultz LD, Pittelkow MR, Grando SA: Antibodies against keratinocyte antigens other than desmoglein 1 and 3 can induce pemphigus vulgaris-like lesions. J Clin Invest. 2000, 106: 1467-1479.","journal-title":"J Clin Invest"},{"key":"57_CR21","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1046\/j.1523-1747.2001.01307.x","volume":"116","author":"JR Stanley","year":"2001","unstructured":"Stanley JR, Nishikawa T, Diaz LA, Amagai M: Pemphigus: is there another half of the story?. J Invest Dermatol. 2001, 116: 489-490. 10.1046\/j.1523-1747.2001.01307.x.","journal-title":"J Invest Dermatol"},{"key":"57_CR22","doi-asserted-by":"publisher","first-page":"6468","DOI":"10.4049\/jimmunol.172.10.6468","volume":"172","author":"C Veldman","year":"2004","unstructured":"Veldman C, Hohne A, Dieckmann D, Schuler G, Hertl M: Type I regulatory T cells specific for desmoglein 3 are more frequently detected in healthy individuals than in patients with pemphigus vulgaris. J Immunol. 2004, 172: 6468-6475.","journal-title":"J Immunol"},{"key":"57_CR23","doi-asserted-by":"publisher","first-page":"3883","DOI":"10.4049\/jimmunol.172.6.3883","volume":"172","author":"CM Veldman","year":"2004","unstructured":"Veldman CM, Gebhard KL, Uter W, Wassmuth R, Grotzinger J, Schultz E, Hertl M: T cell recognition of desmoglein 3 peptides in patients with pemphigus vulgaris and healthy individuals. J Immunol. 2004, 172: 3883-3892.","journal-title":"J Immunol"},{"key":"57_CR24","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1006\/clim.2002.5259","volume":"105","author":"MK Hacker","year":"2002","unstructured":"Hacker MK, Janson M, Fairley JA, Lin MS: Isotypes and antigenic profiles of pemphigus foliaceus and pemphigus vulgaris autoantibodies. Clin Immunol. 2002, 105: 64-74. 10.1006\/clim.2002.5259.","journal-title":"Clin Immunol"},{"key":"57_CR25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1093\/nar\/30.1.35","volume":"30","author":"CH Wu","year":"2002","unstructured":"Wu CH, Huang H, Arminski L, Castro-Alvear J, Chen Y, Hu ZZ, Ledley RS, Lewis KC, Mewes HW, Orcutt BC, Suzek BE, Tsugita A, Vinayaka CR, Yeh LSL, Zhang J, Barker WC: The Protein Information Resource: an integrated public resource of functional annotation of proteins. Nucleic Acids Res. 2002, 30: 35-37. 10.1093\/nar\/30.1.35.","journal-title":"Nucleic Acids Res"},{"key":"57_CR26","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1046\/j.1365-2133.2000.03328.x","volume":"142","author":"CM Proby","year":"2000","unstructured":"Proby CM, Ota T, Suzuki H, Koyasu S, Gamou S, Shimizu N, Wahl JK, Wheelock MJ, Nishikawa T, Amagai M: Development of chimeric molecules for recognition and targeting of antigen-specific B cells in pemphigus vulgaris. Br J Dermatol. 2000, 142: 321-330. 10.1046\/j.1365-2133.2000.03328.x.","journal-title":"Br J Dermatol"},{"key":"57_CR27","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1111\/1523-1747.ep12340738","volume":"109","author":"MS Lin","year":"1997","unstructured":"Lin MS, Swartz SJ, Lopez A, Ding X, Fairley JA, Diaz LA: T lymphocytes from a subset of patients with pemphigus vulgaris respond to both desmoglein-3 and desmoglein-1. J Invest Dermatol. 1997, 109: 734-737. 10.1111\/1523-1747.ep12340738.","journal-title":"J Invest Dermatol"},{"key":"57_CR28","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/BF00175254","volume":"4","author":"J Schleucher","year":"1994","unstructured":"Schleucher J, Schwendinger M, Sattler M, Schmidt P, Schedletzky O, Glaser SJ, Sorensen OW, Griesinger C: A general enhancement scheme in heteronuclear multidimensional NMR employing pulsed field gradients. J Biomol NMR. 1994, 4: 301-306. 10.1007\/BF00175254.","journal-title":"J Biomol NMR"},{"key":"57_CR29","doi-asserted-by":"publisher","first-page":"2970","DOI":"10.1021\/ja003760i","volume":"123","author":"S Schwarzinger","year":"2001","unstructured":"Schwarzinger S, Kroon GJA, Foss TR, Chung J, Wright PE, Dyson HJ: Sequence-dependent correction of random coil NMR chemical shifts. J Am Chem Soc. 2001, 123: 2970-2978. 10.1021\/ja003760i.","journal-title":"J Am Chem Soc"},{"key":"57_CR30","volume-title":"Methods in Molecular Biology","author":"GE Morris","year":"1996","unstructured":"Morris GE: Epitope Mapping Protocols. Methods in Molecular Biology. 1996, Humana Press: Totowa, NJ"},{"key":"57_CR31","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0092-8674(90)90222-Z","volume":"61","author":"A Nose","year":"1990","unstructured":"Nose A, Tsuji K, Takeichi M: Localisation of specificity determining sites in cadherin cell adhesion molecules. Cell. 1990, 61: 147-155. 10.1016\/0092-8674(90)90222-Z.","journal-title":"Cell"},{"key":"57_CR32","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1172\/JCI115968","volume":"90","author":"M Amagai","year":"1992","unstructured":"Amagai M, Karpati S, Prussick R, Klaus-Kovtun V, Stanley JR: Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic. J Clin Invest. 1992, 90: 919-926.","journal-title":"J Clin Invest"},{"key":"57_CR33","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1038\/labinvest.3700167","volume":"84","author":"MS Lim","year":"2004","unstructured":"Lim MS, Elenitoba-Johnson KSJ: Proteomics in pathology research. Lab Invest. 2004, 84: 1227-1244. 10.1038\/labinvest.3700167.","journal-title":"Lab Invest"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1479-5876-2-43.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1479-5876-2-43\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1479-5876-2-43.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T12:23:31Z","timestamp":1728303811000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/1479-5876-2-43"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,11]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2004,12]]}},"alternative-id":["57"],"URL":"https:\/\/doi.org\/10.1186\/1479-5876-2-43","relation":{},"ISSN":["1479-5876"],"issn-type":[{"type":"electronic","value":"1479-5876"}],"subject":[],"published":{"date-parts":[[2004,12,11]]},"assertion":[{"value":"15 October 2004","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2004","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2004","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"43"}}