SummaryWe have previously described the isolation of a cDNA clone, designated NKG2, that was expressed in all natural killer (NK) cells tested but not in T or B cells . In the present communication, the original isolate, when used to probe a cDNA library prepared from a CD3 -NK cell clone, was found to crosshybridize with a family of transcripts that fell into four distinct groups designated NKG2-A, -B, -C, and -D. Full-length cDNA sequences were determined for each group, and the DNA and inferred peptide sequences were analyzed. All four transcripts encode type II membrane proteins of 215-233 amino acids. NKG2-A and -B peptides appear to be alternative splicing products of a single gene. NKG2-C is highly homologous with group A, having 94% homology in the external (COOH-terminal) domain and 56% homology throughout the internal and transmembrane regions . NKG2-D is distantly but significantly related (21% amino acid homology) to the first three groups . Therefore, NKG2-A, -C, and -D appear to be encoded by distinct genes within a family of NK cell-specific genes . Peptide sequence homology searches demonstrate that the NKG2 peptides are members of a supergene family that includes several other type II membrane proteins . This family is characterized by the presence of a C-type animal lectin domain, and several of its members have demonstrated transmembrane signaling capability. N K cells appear to be closely related to T cells based upon the common expression of a number of cell type-specific transcripts and cell surface antigens (1, 2). NK cells and T cells also share expression of perforin and serine proteases, components of the cytolytic machinery that are found almost exclusively in lytic cells . However, the TCR/CD3 complex responsible for triggering lytic activity in T cells is absent from NK cells, and a corresponding structure that recognizes the NK target antigen and triggers NK lytic activity has not been identified . Elucidation of these structures would greatly facilitate an understanding of the in vivo function of NK cells.We initiated a project to identify, through the use of differential hybridization and cDNA subtraction methodology, genes that are expressed preferentially in NK cells, with particular emphasis on those encoding membrane-bound proteins (1). In an earlier report, we identified 12 groups of crosshybridizing cDNA clones that were expressed in NK cells but not in an EBV transformed B cell line. One of these groups, NK group 2 (NKG2), was expressed only in NK cells among the panel of cells that we examined . In the current paper, we report that NKG2 is comprised of a group of related transcripts that encode a series of type 11 membrane proteins.
Materials and MethodsA cDNA library was prepared from B22, a CD3-, CD16 -, CD56 + human NK clone that lyres K562 (1) . The library was probed with the previously described NKG2 isolate (1) to find additional cDNA clones. DNA sequences of NKG2-A, -B, and -C were determined on templates derived from the original X-Gem cDNA clones via the asymmetr...