{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:11:49Z","timestamp":1789009909246,"version":"build-2803163510"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,10]]},"abstract":"<jats:p>\n                    T cell recognition of minor histocompatibility antigens (mHags) underlies allogeneic immune responses that mediate graft-versus-host disease and the graft-versus-leukemia effect following stem cell transplantation. Many mHags derive from single amino acid polymorphisms in MHC-restricted epitopes, but our understanding of the molecular mechanisms governing mHag immunogenicity and recognition is incomplete. Here we examined antigenic presentation and T-cell recognition of HA-1, a prototypic autosomal mHag derived from single nucleotide dimorphism (\n                    <jats:italic>\n                      HA-1\n                      <jats:sup>H<\/jats:sup>\n                    <\/jats:italic>\n                    versus\n                    <jats:italic>\n                      HA-1\n                      <jats:sup>R<\/jats:sup>\n                    <\/jats:italic>\n                    ) in the\n                    <jats:italic>HMHA1<\/jats:italic>\n                    gene. The HA-1\n                    <jats:sup>H<\/jats:sup>\n                    peptide is restricted by HLA-A2 and is immunogenic in\n                    <jats:italic>\n                      HA-1\n                      <jats:sup>R\/R<\/jats:sup>\n                    <\/jats:italic>\n                    into\n                    <jats:italic>\n                      HA-1\n                      <jats:sup>H<\/jats:sup>\n                    <\/jats:italic>\n                    transplants, while\n                    <jats:italic>\n                      HA-1\n                      <jats:sup>R<\/jats:sup>\n                    <\/jats:italic>\n                    has been suggested to be a \u201cnull allele\u201d in terms of T cell reactivity. We found that proteasomal cleavage and TAP transport of the 2 peptides is similar and that both variants can bind to MHC. However, the His&gt;Arg change substantially decreases the stability and affinity of HLA-A2 association, consistent with the reduced immunogenicity of the HA-1\n                    <jats:sup>R<\/jats:sup>\n                    variant. To understand these findings, we determined the structure of an HLA-A2-HA-1\n                    <jats:sup>H<\/jats:sup>\n                    complex to 1.3\u212b resolution. Whereas His-3 is accommodated comfortably in the D pocket, incorporation of the lengthy Arg-3 is predicted to require local conformational changes. Moreover, a soluble TCR generated from HA-1\n                    <jats:sup>H<\/jats:sup>\n                    -specific T-cells bound HA-1\n                    <jats:sup>H<\/jats:sup>\n                    peptide with moderate affinity but failed to bind HA-1\n                    <jats:sup>R<\/jats:sup>\n                    , indicating complete discrimination of HA-1 variants at the level of TCR\/MHC interaction. Our results define the molecular mechanisms governing immunogenicity of HA-1, and highlight how single amino acid polymorphisms in mHags can critically affect both MHC association and TCR recognition.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0900411106","type":"journal-article","created":{"date-parts":[[2009,2,21]],"date-time":"2009-02-21T22:33:01Z","timestamp":1235255581000},"page":"3889-3894","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition"],"prefix":"10.1073","volume":"106","author":[{"given":"Sarah","family":"Nicholls","sequence":"first","affiliation":[{"name":"Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen P.","family":"Piper","sequence":"additional","affiliation":[{"name":"Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiyaz","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Dafforn","sequence":"additional","affiliation":[{"name":"School of Biosciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Tenzer","sequence":"additional","affiliation":[{"name":"Johannes-Gutenberg Universit\u00e4t Mainz, Institut f\u00fcr Immunologie, Hochhaus am Augustusplatz, 55131 Mainz, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboob","family":"Salim","sequence":"additional","affiliation":[{"name":"Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Premini","family":"Mahendra","sequence":"additional","affiliation":[{"name":"Department of Haematology, University Hospital Birmingham NHS Foundation Trust, Birmingham B15 2TH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Craddock","sequence":"additional","affiliation":[{"name":"Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences,"},{"name":"Department of Haematology, University Hospital Birmingham NHS Foundation Trust, Birmingham B15 2TH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van Endert","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U580, Paris, France; Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine Ren\u00e9 Descartes, Paris, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansj\u00f6rg","family":"Schild","sequence":"additional","affiliation":[{"name":"Johannes-Gutenberg Universit\u00e4t Mainz, Institut f\u00fcr Immunologie, Hochhaus am Augustusplatz, 55131 Mainz, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cobbold","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor H.","family":"Engelhard","sequence":"additional","affiliation":[{"name":"Carter Immunology Center and Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A. H.","family":"Moss","sequence":"additional","affiliation":[{"name":"Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences,"},{"name":"Department of Haematology, University Hospital Birmingham NHS Foundation Trust, Birmingham B15 2TH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin E.","family":"Willcox","sequence":"additional","affiliation":[{"name":"Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35077251"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1365"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.3.555.555"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.8.2120.2120"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(03)00190-5"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5353.1054"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03536.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0530192100"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404056"},{"key":"e_1_3_3_10_2","first-page":"1415","article-title":"Adult and cord blood T cells can acquire HA-1 specificity through HA-1 T-cell receptor gene transfer","volume":"90","author":"Mommaas B","year":"2005","unstructured":"B Mommaas, et al., Adult and cord blood T cells can acquire HA-1 specificity through HA-1 T-cell receptor gene transfer. 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