{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,1,7]],"date-time":"2024-01-07T00:01:35Z","timestamp":1704585695788},"reference-count":36,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>T-cell receptors (TCRs) of a series of minor histocompatibility antigen (mHag) HA-1\u2013specific cytotoxic T-cell (CTL) clones isolated from 3 unrelated patients have been shown to use the same BV6S4A2 segment with conserved amino acids in the CDR3V\u03b2 region. This suggests that different HA-1\u2013specific TCRs interact similarly to the HA-1 antigen presented by the HLA-A2 molecule. The mHag HA-1 forms an immunogenic complex with HLA-A2 and induces strong alloimmune responses after stem cell transplantation (SCT). It was questioned, therefore, whether clonal and polyclonal HA-1\u2013specific CTL responses can be antagonized by a single TCR antagonistic peptide. Functional analysis and molecular modeling of single and double amino acid substitutions of TCR contact residues, adjacent residues, and HLA-A2 binding residues resulted in 4 peptides with high affinity for HLA-A2 and with the capacity to inhibit the lysis of endogenously HA-1\u2013expressing EBV-BLCL by 3 different HA-1\u2013specific CTL clones. These peptides also efficiently antagonized HA-1\u2013specific polyclonal CTL lines derived from 3 patients and significantly reduced the number of interferon-\u03b3\u2013producing HA-1\u2013specific CTL of a patient with graft-versus-host disease after HA-1\u2013mismatched SCT. These data show that general TCR antagonists can be developed that inhibit HLA-A2\u2013restricted HA-1\u2013specific CTL responses on the clonal and the polyclonal level and that TCR antagonists may modulate the immunodominant mHag HA-1 responses.<\/jats:p>","DOI":"10.1182\/blood.v99.3.985","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"985-992","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":9,"title":["General T-cell receptor antagonists to immunomodulate HLA-A2\u2013restricted minor histocompatibility antigen HA-1\u2013specific T-cell responses"],"prefix":"10.1182","volume":"99","author":[{"given":"Joke M. M.","family":"den Haan","sequence":"first","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, and the Department of Medicinal Chemistry, Leiden University, Leiden\/Amsterdam Center for Drug Research, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuna","family":"Mutis","sequence":"additional","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, and the Department of Medicinal Chemistry, Leiden University, Leiden\/Amsterdam Center for Drug Research, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"Blokland","sequence":"additional","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, and the Department of Medicinal Chemistry, Leiden University, Leiden\/Amsterdam Center for Drug Research, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ad P.","family":"IJzerman","sequence":"additional","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, and the Department of Medicinal Chemistry, Leiden University, Leiden\/Amsterdam Center for Drug Research, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"Goulmy","sequence":"additional","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, and the Department of Medicinal Chemistry, Leiden University, Leiden\/Amsterdam Center for Drug Research, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021217192476600_B1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/384134a0","article-title":"Structure of the complex between human T-cell receptor, viral 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