NONSPECIFIC CYTOTOXIC-CELL RECEPTOR PROTEIN-1 - A NOVEL (PREDICTED) TYPE-III MEMBRANE-RECEPTOR ON THE TELEOST EQUIVALENT OF NATURAL-KILLER-CELLS RECOGNIZES CONVENTIONAL ANTIGEN

The phylogenetic model for ''conventional'' antigen recognition by NK cells may be a protein (NCCRP-1) recently identified from catfish nons pecific cytotoxic cells (NCC). NCCRP-1 may be a Type III membrane prot ein. The antigen binding domain was identified by competition experime nts using synthetic peptides. Within this domain, a 38-mer peptide (aa 104-140) inhibited NCC killing of IM-9, HL-60, NC-37, U937. and MOLT- 4 target cells. Biotinylated 38-mer also bound to IM-9 target cells. A mab which inhibited conjugate formation between NCC and target cells also bound to the 38-mer. Nonbiotinylated 38-mer inhibited mab 5C6 bin ding to immobilized homologous biotinylated peptide in cold competitio n ELISA experiments. peptide 104-140 was truncated into two peptides. Amino acid 104-119 bound to (68%) and inhibited lyis of IM-9 target ce lls, whereas aa 120-140 had no activity. A predicted structure-functio n algorithm suggested an N-terminal domain containing BOX-1 motifs for cytokine activation; a C-terminal domain containing abundant phosphor ylation sites (i.e., Y, S, and T amino acids); and an extracellular an tigen binding domain. (C) 1998 Academic Press.