The expression of protein antigens on the surface of nematodes is modulated by environmental signals (surface antigen switching). In the free-living nematode Caenorhabditis elegans, an antigen displayed on the L1 surface is induced on later larval stages under altered growth conditions. Mutations in certain C. elegans genes affect this switch; some mutants display the L1 antigen constitutively at all larval stages, regardless of conditions, while others with chemosensory defects are unable to switch on the antigen at the later stages. The long-term goal of this application is to understand how these genes Control timing of surface antigen expression. Gene srf-6 appears to play a pivotal role in surface antigen switching. A genomic DNA fragment containing a srf-6 candidate gene has been identified. The candidate gene appears to encode a membrane protein. Temporal and spatial patterns of srf-6 gene expression will be studied by Northern blotting, RT-PCR, and in vivo expression of transgenic srf- 6::green fluorescent protein fusion constructs. Expression of genes flanking srf-6 will be studied to determine whether srf-6 transcription is regulated as part of an operon. The DNA sequence of mutant srf-6 alleles will be determined. Previously identified chemosensory mutants will be tested for surface antigen switching defects. Order of gene action in surface antigen switching will be studied by epistasis. Neurons important for surface antigen switching will be identified by disruption of specific cells with a mutant cell-death gene. Certain genes that affect surface antigen switching have homologs in a variety of intercellular signaling pathways, including those based on seven-transmembrane domain and guanylyl cyclase receptors. Studying C. elegans surface antigen switching may help understand these processes. Surface antigen switching may be responsible for the ability of parasitic nematodes to evade host immune responses. Such parasitic infections are a severe global public health problem. Developmental similarities between nematodes suggest that studying C. elegans surface antigen switching will help understand similar mechanisms in parasitic nematodes.
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