{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T10:40:17Z","timestamp":1759401617404},"reference-count":33,"publisher":"Proceedings of the National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,7,9]]},"abstract":"<jats:p>We have previously identified an antigen (Ag) recognized on a human large cell carcinoma of the lung by a tumor-specific cytotoxic T lymphocyte clone derived from autologous tumor infiltrating lymphocytes (TILs). The antigenic peptide is presented by HLA-A2 molecules and is encoded by a mutated \u03b1<jats:italic>-actinin-4<\/jats:italic>(<jats:italic>ACTN4<\/jats:italic>) gene. In the present report, we have isolated two anti-\u03b1-actinin-4 T cell clones from the same patient TIL and from his peripheral blood lymphocytes (PBLs) by using tetramers of soluble HLA-A2 molecules loaded with the mutated peptide. Although all of the clones displayed similar tetramer labeling, those isolated from PBL showed lower avidity of Ag recognition and killed the specific target much less efficiently, indicating that tetramer staining does not correlate with clone avidity\/tumor reactivity. T cell receptor (TCR) analysis revealed that \u03b1-actinin-4-reactive clones used distinct \u03b1 and \u03b2 chain rearrangements, demonstrating TCR repertoire diversity. Interestingly, TCR\u03b2 chain gene usage indicated that only Ag-specific clones with high functional avidity were expanded at the tumor site, whereas a low-avidity clone was exclusively amplified in patient peripheral blood. Our results point to the existence of distinct but overlapping antitumor TCR repertoires in TIL and PBL and suggest a selective<jats:italic>in situ<\/jats:italic>expansion of tumor-specific cytotoxic T lymphocyte with high avidity\/tumor reactivity.<\/jats:p>","DOI":"10.1073\/pnas.142308199","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T22:26:28Z","timestamp":1027895188000},"page":"9358-9363","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["Cytotoxic T lymphocytes directed against a tumor-specific mutated antigen display similar HLA tetramer binding but distinct functional avidity and tissue distribution"],"prefix":"10.1073","volume":"99","author":[{"given":"Hamid","family":"Echchakir","sequence":"first","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut Gustave Roussy, Institut F\u00e9d\u00e9ratif de Recherche-54, F-94805 Villejuif, Cedex, France"}]},{"given":"Guillaume","family":"Doroth\u00e9e","sequence":"additional","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut Gustave Roussy, Institut F\u00e9d\u00e9ratif de Recherche-54, F-94805 Villejuif, Cedex, France"}]},{"given":"Isabelle","family":"Vergnon","sequence":"additional","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut Gustave Roussy, Institut F\u00e9d\u00e9ratif de Recherche-54, F-94805 Villejuif, Cedex, France"}]},{"given":"Jeanne","family":"Menez","sequence":"additional","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut Gustave Roussy, Institut F\u00e9d\u00e9ratif de Recherche-54, F-94805 Villejuif, Cedex, France"}]},{"given":"Salem","family":"Chouaib","sequence":"additional","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut Gustave Roussy, Institut F\u00e9d\u00e9ratif de Recherche-54, F-94805 Villejuif, Cedex, France"}]},{"given":"Fathia","family":"Mami-Chouaib","sequence":"additional","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut Gustave Roussy, Institut F\u00e9d\u00e9ratif de Recherche-54, F-94805 Villejuif, Cedex, France"}]}],"member":"341","published-online":{"date-parts":[[2002,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80050-7"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990118)80:2<219::AID-IJC10>3.0.CO;2-S"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.11.1669"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/12.4.537"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.11.6057"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.1.9805073"},{"key":"e_1_3_3_7_2","first-page":"2731","volume":"54","author":"Slingluff C L","year":"1994","unstructured":"C L Slingluff, A L Cox, J M Stover, M M Moore, D F Hunt, V H Engelhard Cancer Res 54, 2731\u20132737 (1994).","journal-title":"Cancer Res"},{"key":"e_1_3_3_8_2","first-page":"3387","volume":"54","author":"Yoshino I","year":"1994","unstructured":"I Yoshino, P S Goedegebuure, G E Peoples, A S Parikh, J M DiMaio, H K Lyerly, A F Gazdar, T J Eberlein Cancer Res 54, 3387\u20133390 (1994).","journal-title":"Cancer Res"},{"key":"e_1_3_3_9_2","first-page":"5144","volume":"58","author":"Hogan K T","year":"1998","unstructured":"K T Hogan, D P Eisinger, S B Cupp, K J Lekstrom, D D Deacon, J Shabanowitz, D F Hunt, V H Engelhard, C L Slingluff, M M Ross Cancer Res 58, 5144\u20135150 (1998).","journal-title":"Cancer Res"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.4049\/jimmunol.163.9.4994","volume":"163","author":"Gomi S","year":"1999","unstructured":"S Gomi, M Nakao, F Niiya, Y Imamura, K Kawano, S Nishizaka, A Hayashi, Y Sobao, K Oizumi, K Itoh J Immunol 163, 4994\u20135004 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_11_2","first-page":"3550","volume":"60","author":"Kawano K","year":"2000","unstructured":"K Kawano, S Gomi, K Tanaka, N Tsuda, T Kamura, K Itoh, A Yamada Cancer Res 60, 3550\u20133558 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_3_12_2","first-page":"3718","volume":"61","author":"Karanikas V","year":"2001","unstructured":"V Karanikas, D Colau, J F Baurain, R Chiari, J Thonnard, I Gutierrez-Roelens, C Goffinet, E V Van Schaftingen, P Weynants, T Boon, et al. Cancer Res 61, 3718\u20133724 (2001).","journal-title":"Cancer Res"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5284.94"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70161-7"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/9525"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.9.1641"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.1.533"},{"key":"e_1_3_3_18_2","first-page":"2047","volume":"61","author":"Dietrich P Y","year":"2001","unstructured":"P Y Dietrich, P R Walker, A L Quiquerez, G Perrin, V Dutoit, D Li\u00e9nard, P Guillaume, J C Cerottini, P Romero, D Valmori Cancer Res 61, 2047\u20132054 (2001).","journal-title":"Cancer Res"},{"key":"e_1_3_3_19_2","first-page":"4078","volume":"61","author":"Echchakir H","year":"2001","unstructured":"H Echchakir, F Mami-Chouaib, I Vergnon, J F Baurain, V Karanikas, S Chouaib, P G Coulie Cancer Res 61, 4078\u20134083 (2001).","journal-title":"Cancer Res"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203310"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19980703)77:1<7::AID-IJC2>3.0.CO;2-Y"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(86)90322-4"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(89)90397-9"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830220522"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(95)80117-0"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.4049\/jimmunol.153.6.2807","volume":"153","author":"Puisieux I","year":"1994","unstructured":"I Puisieux, J Even, C Pannetier, F Jotereau, M Favrot, P Kourilsky J Immunol 153, 2807\u20132818 (1994).","journal-title":"J Immunol"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200102)31:2<412::AID-IMMU412>3.0.CO;2-4"},{"key":"e_1_3_3_28_2","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.4049\/jimmunol.162.4.2227","volume":"162","author":"Yee C","year":"1999","unstructured":"C Yee, P A Savage, P P Lee, M M Davis, P D Greenberg J Immunol 162, 2227\u20132234 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_29_2","first-page":"5850","volume":"61","author":"Dutoit V","year":"2001","unstructured":"V Dutoit, V Rubio-Godoy, P Y Dietrich, A L Quiqueres, V Schnuriger, D Rimoldi, D Li\u00e9nard, D Speiser, P Guillaume, P Batard, et al. Cancer Res 61, 5850\u20135856 (2001).","journal-title":"Cancer Res"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181348898"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.3.1167"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5824"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.8.4231"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.142308199","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T23:40:15Z","timestamp":1682293215000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.142308199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,7]]},"references-count":33,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2002,7,9]]}},"alternative-id":["10.1073\/pnas.142308199"],"URL":"https:\/\/doi.org\/10.1073\/pnas.142308199","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,7]]},"assertion":[{"value":"2002-02-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-05-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}