The main thrust of this laboratory is to develop experimental approaches to the study of leukemia founded on immunogenetic principles that might be helpful in achieving progress toward the control or elimination of leukemia in man. We seek to address the following specific goals. (1) Study viral sequences flanking MHC genes and their interactions with Class I genes. To do so we shall (a) clone at least one viral genome located in the TL region and prepare a single copy molecular probe and monoclonal antibodies specific for this virus; (b) sequence portions of the H-2 gene flanking the viral genome cloned, so that a synthetic oligonucleotide probe specific for this H-2 gene can be made and its expression studied and (c) examine other Class I gene regions in C57BL/10 mouse cells and all Class I gene regions in BALB/c mouse cells for flanking viral sequences. (2) Clone minor histocompatibility gene H-30 (and possibly H-34). To accomplish this goal we shall: (a) For H-30 cloning, prepare and screen a cosmid library from a Chinese hamster x mouse somatic cell line containing only murine chromsomes 2, 14, and 17 (H-30 is on chromosome 2) with a 358 bp viral probe derived from the H-30 region; (b) develop cytolytic killer cells (CTL) to assay for the H-30 gene product in transfectants generated by transformation of mouse fibroblasts with DNA derived from putative H-30 region cosmid clones, and (c) for H-34 cloning screen available cloned chromosome 12 derived segments of genomic DNA for H-34 by transfection and CTL assay. The intial experiments, will permit us to begin to address important features regarding the evolutionary implications to host and virus of the current observations and allow cloning of minor H genes for the first time.
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