TWENTY-THIRD ANNUAL EASTERN FISH HEALTH WORKSHOP JOHN CARVER INN, PLYMOUTH, MA 30 MARCH - 2 APRIL, 1998 Fine Specificity Of The Antigen Recognition Receptor On Nonspecific Cytotoxic Cells From Catfish. Donald L. Evans and L. Jaso-Friedmann Department of Medical Microbiology and Parasitology, University of Georgia, Athens, GA. 30602. Mammalian NK cells recognize alloantigen as well as conventional antigen. Binding to class-I histocompatibility antigen down modulates NK cytotoxicity. Inhibitory responses are receptor mediated and the fine specificity of certain of the immunoregulatory receptors has been defined. The phylogenetic predecessor of mammalian NK cells may be nonspecific cytotoxic cells (NCC). Both NK and NCC participate in providing innate cytotoxic responses against tumor cells and protozoan parasites. The diversity of different target cells recognized by NCC suggests promiscuous antigen recognition capabilities similar to mammalian lymphokine activated killer cells. Alloantigen immunoregulation of NCC has not been demonstrated. Recently we described an antigen receptor (NCC receptor protein-1/NCCRP-1) which recognizes conventional antigen on tumor cells and on the protozoan Tetrahymena pyriformis. NCCRP-1 may be a type III membrane protein. This predicted membrane conformation is based on synthetic peptide binding studies demonstrating NCCRP-1 peptide binding to susceptible target cells and inhibition of cytotoxicity. To further characterize the participation of NCCRP-1/NCC in innate cytotoxic immunity, the antigen recognized by this receptor was identified and sequenced (e.g. natural killer target antigen/NKTag). NKTag is a 46 kDa protein which is expressed on protozoan parasites and on many different NCC (and NK) sensitive tumor target cells. To confirm the recognition of conventional antigen (i.e. NKTag) by NCCRP-1, sequence specific antisense (AS) oligodeoxynucleotides were applied to either NCC or Tetrahymena. NCC treated with NCCRP-1 AS oligos had significantly reduced NCCRP-1 expression and inhibited cytotoxicity. Tetrahymena treated with NKTag AS oligos had significantly reduced membrane expression of NKTag and did not compete with tumor target cells for cytotoxicity. These studies demonstrated that NCC recognize conventional antigen on tumor cells and protozoan parasites. This interaction may be the principal pathway of initiation of cytotoxic innate immunity in catfish.   Return to 23rd Annual Eastern Fish Health Workshop Return to Leetown Science Center Home Page