DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells.

Abstract

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...

Collectins — soluble proteins containing collagenous regions and lectin domains — and their roles in innate immunity

“…Therefore, although the requirement for hydroxyl-groups of the mannose-or galactose-type within the binding-site on the carbohydrate molecules is determined by the E-N/Q-D pair of residues, other differences seen in the sequences of the lectin domains, and of the extensive loop carrying the binding sites in particular, seem to be also involved in ligand selection in the in vivo interaction of C-type lectins with complex carbohydrate structures. Domains identified by sequence comparison and predicted to have an overall folding similar to that seen in the crystal structure of the C-type lectin domain of MBP (Weis et al, 1991b), but lacking some of the characteristic residues involved in calcium/carbohydrate binding, are seen in a number of type I1 membrane proteins ( QPD-E-WND gal Tanaka et al, 1988 QPD-E-WND gal Zimmerman & Ruoslahti, 1989 QPD-E-WND gal Drickamer, 1981Spiess & Lodish, 1985Drickamer et al, 1984Ii et al, 1990Hoyle & Hill, 1991Sat0 et al, 1992Curtis et al, 1992Suter et al, 1987Yokoyama et al, 1989Chan & Takei, 1989Giorda et al, 1990Van Hoegen et al, 1990Houchins et al, 1991Wong et al, 1991Yoshimatsu et al, 1992Lee et al, 1991Taylor et al, 1989Drickamer et al, 1986White et al, 1985Benson et al, 1985Rust et al, 1991Holmskov et al, 1993bHolmskov et al, 1993aLasky et al, 1989Bevilacqua et al, 1991Johnson et al, 1989Christa et al, 1994Ng & Hew, 1992Ewart et al, 1992Rouquier et al, 1991Taylor et al, 1990 EPN-E-WND man (Drickamer, 1992). Not all of the carbohydrate specificities have been determined (*), and certain proteins, although a Proteins containing C-type lectin domains or regions w...…”

The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region

“…Among these are the CD94/NKG2, the Ly49 and the NKR-P1 families. Whereas members of the CD94/NKG2 and the NKR-P1 families have been found to be expressed in mice, [17][18][19] rats 20 and humans, 5,[21][22][23][24] expression of functional Ly49 proteins has so far only been detected in rodents. 15,19 Recently, an aberrantly spliced cDNA coding for a human LY49 molecule (named Ly49L) has been detected 25 in the expressed sequence tags (EST) database and in cDNA libraries derived from human NK cells.…”

AICL: a new activation-induced antigen encoded by the human NK gene complex

“…Indeed, genes encoding four different type II proteins/protein families with C-type lectin domains have been located on the human chromosome 12. These are the NKG2 family (Houchins et al 1991), NKR-P1A (Lanier et al 1994), CD94 (Chang et al 1995), and CD69 Ziegler et al 1993;Lopez-Cabrera et al 1993). Localization of the CD69 gene in the NK gene complex has been surprising, since function of this molecule is not restricted to NK cells.…”