Somatic Cell Genetics, Vol. 1, No. 2, 1975, pp. 123-136 Cell-Mediated Immunoselection Against Ceil-Surface Antigens of Somatic Cell Hybrids Barbara B. Knowles and Katherine Swift The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania Received 3 November 1974--Final 5 December 1975 Abstract--Cytotoxic lymphoid cells derived from in vivo immunization of mice across H2 barriers were utilized in in vitro cytotoxicity assays. The target cells were somatic cell hybrids derived from parental cells differing at the H2 locus. The hybrid cells surviving cytotoxicity were grown to confluent populations and the H2 antigens selected against were no longer demonstrable by indirect immunofluorescence. Comparative karyology of hybrid cells ex- pressing both parental H2 types before immunoselection with hybrid cells sur- viving immunoselection revealed a decrease in the number of murine chromosomes number 17, suggesting that those cells surviving cytotoxicity had spontaneously lost these chromosomes prior to the selection event. The pos- sibility of immunoconstruction of somatic cell hybrids on the basis of their cell- surface antigens is discussed. INTRODUCTION Somatic cell hybrids with specific chromosome exclusions can be selected by immunologic cytotoxicity. Complement-mediated antibody destruction of interspecific hybrid cells expressing antigenic determinants, with survival of nonreactive cells, has already been described. The mechanism of this immunoselection appears to be enrichment of a preexist- ing population of hybrid cells deficient in chromosome coding for the sen- sitizing antigen. Because of this deficiency, these cells escape the cytotoxic reaction (1, 2). Evidence is presented that histocompatibility antigens of in- traspecific somatic cell hybrids are suitable targets for cell-mediated im- munoselection. MATERIALS AND METHODS Tissue Culture and Cells. All cells were grown in Eagle's minimal es- sential medium (MEM) (Auto Pow, Flow Laboratories) supplemented with 123 9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission of the publisher.