{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:20:52Z","timestamp":1759332052044},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":7260,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1986,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Two experimental systems have demonstrated somatic variation of antigen recognition specificity of long\u2010term cytotoxic T cell (CTL) clones. System 1 used CTL clone BT7.4.1 with strict specificity for K<jats:sup>b<\/jats:sup>\/TNP, which had been continuously cultured for 15 months in the presence of H\u20102<jats:sup>b<\/jats:sup>\/TNP stimulator cells and interleukin 2. Upon removal of the TNP antigen from the cultures, 99% of the clone cells within about 10 cell divisions lost their ability to grow in the presence of antigen and interleukin 2 (lethal variants). Of the surviving 1%, about 60% retained the ability to lyse target cells in the presence of lectins but only 12% could be considered as \u201cwild type\u201d BT7.4.1 cells, <jats:italic>i.e.<\/jats:italic> they still specifically lysed H\u20102<jats:sup>b<\/jats:sup>\/TNP\u2010bearing target cells. The majority of the growing cells, thus, had to be considered as specificity loss variants. Several specificity loss variants were established in culture and were shown to express membrane\u2010bound T cell \u201creceptor\u201d heterodimer similar to their TNP\u2010specific ancester, BT7.4.1. Principally the same types of variants were generated in cultures growing in the presence of TNP antigen, although in quantitatively reduced numbers. Under these conditions the specific stimulator cells appeared to impose a significant selective advantage for \u201cwild type\u201d CTL since even after 15 months the cultures fully retained their specificity for the nominal antigen.<\/jats:p><jats:p>In system 2, the development of cytolytic fine specificity of a panel of 42 individual K<jats:sup>b<\/jats:sup>\/TNP\u2010specific CTL clones was followed over a period of 8 months of <jats:italic>in vitro<\/jats:italic> culture. At the beginning of the test, 37 of these clones exhibited significant cross\u2010reactivity for lysis of H\u20102<jats:sup>k<\/jats:sup>\/TNP target cells. This number of cross\u2010reactive clones continuously diminished with time and dropped to only 4 clones after 8 months in culture. All 42 clones retained their original K<jats:sup>b<\/jats:sup>\/TNP specificity and after losing their reactivity for H\u20102<jats:sup>k<\/jats:sup>\/TNP usually showed no decrease but rather an increase in their cytotoxic activity towards K<jats:sup>b<\/jats:sup>\/TNP target cells. Loss of H\u20102<jats:sup>k<\/jats:sup>\/TNP cross\u2010reactivity was not accompanied by loss of Lyt\u20102 or of LFA\u20101 surface antigens or by loss of sensitivity of the cytotoxicity to inhibition by anti\u2010Lyt\u20102 or by anti\u2010LFA\u20101 antibody.<\/jats:p><jats:p>We conclude from these observations that <jats:italic>in vitro<\/jats:italic> cultivated CTL clones, at least those of C57BL\/6 anti\u2010TNP\u2010C57BL\/6 specificity, are not stable in terms of their antigen recognition specificity. Despite this instability, their nominal cytolytic specificity can be maintained over long periods of <jats:italic>in vitro<\/jats:italic> culture and even a maturation to increased antigen specificity is regularly observed, provided antigen is present in the cultures. We assume this indicates that maintenance of clonal specificity <jats:italic>in vitro<\/jats:italic> is a matter of antigen\u2010induced selection rather than a consequence of structural stability of the antigen receptor.<\/jats:p>","DOI":"10.1002\/eji.1830160608","type":"journal-article","created":{"date-parts":[[2007,2,28]],"date-time":"2007-02-28T23:25:35Z","timestamp":1172705135000},"page":"631-639","source":"Crossref","is-referenced-by-count":16,"title":["Hapten\u2010specific cytotoxic T cell clones undergo somatic variation of their antigen recognition specificity"],"prefix":"10.1002","volume":"16","author":[{"given":"Hans Ulrich","family":"Weltzien","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Kempkes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dragana L.","family":"Jankovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Eichmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.01.040183.003221"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1980.tb00326.x"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830101106"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.01.040183.001421"},{"key":"e_1_2_1_6_2","doi-asserted-by":"crossref","first-page":"584","DOI":"10.4049\/jimmunol.132.2.584","volume":"132","author":"Shortman K.","year":"1984","journal-title":"J. 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