Faculty Research 1990 - 1999

Gene mapping in a murine cell line by immunoselection with cytotoxic T lymphocytes.

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Animal, Antigens-CD: bi, ge, Cell-Line-Transformed, Chromosome-Mapping: mt, Cytotoxicity-Immunologic, Female, Genes-Structural, Heterozygote, Karyotyping, Male, Mice: ge, Mice-Inbred-C57BL, Mutation, Selection-(Genetics), Sequence-Deletion, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes-Cytotoxic: im

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Genomics 1994 Jan 15;19(2):273-9


CA34196/CA/NCI, AI28802/AI/NIAID, AI24424/AI/NIAID


Minor histocompatibility (H) loci encode alloantigens that are recognized by cytotoxic T (Tc) lymphocytes. A (C57BL/10 x 129)F1-derived transformed lymphocyte cell line was immunoselected in vitro with cloned Tc cells that were specific for H-3aa, a Chromosome 2-encoded minor H antigen. This cell line is heterozygous at H-3a (former symbol, Cd-1) and other loci. Three groups of antigen-loss variants were identified. One group contained mutations affecting only the antigen-encoding gene. Another group probably arose through a single homologous interchromosomal exchange, resulting in extensive regions of loss of heterozygosity (LOH). The third group of variants contained an interstitial LOH, one of which was shown to be a significant deletion. Several deletion boundaries were identified, one of which ordered the closely linked H-3a and beta 2-microglobulin (B2m) genes. We suggest that Tc immunoselection against minor H antigens is a promising approach for targeting negative selection to specified chromosomal regions and can provide high-resolution genetic map information.

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