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L Morelli

Publications and source records attributed to L Morelli.

At least 37 records · Page 2Linked to original sources
PubMed1998

Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity.

NKp46 has been shown to represent a novel, natural killer (NK) cell-specific surface molecule, involved in human NK cell activation. In this study, we further analyzed the role of NKp46 in natural cytotoxicity against different tumor target cells. We provide direct evidence that NKp46 represents a major activating receptor involved in the recognition and lysis of both human and murine tumor cells. Although NKp46 may cooperate with other activating receptors (including the recently identified NKp44 molecule) in the induction of NK-mediated lysis of human tumor cells, it may represent the only human NK receptor involved in recognition of murine target cells. Molecular cloning of the cDNA encoding the NKp46 molecule revealed a novel member of the immunoglobulin (Ig) superfamily, characterized by two C2-type Ig-like domains in the extracellular portion. The transmembrane region contains the positively charged amino acid Arg, which is possibly involved in stabilizing the association with CD3zeta chain. The cytoplasmic portion, spanning 30 amino acids, does not contain immunoreceptor tyrosine-based activating motifs. Analysis of a panel of human/hamster somatic cell hybrids revealed segregation of the NKp46 gene on human chromosome 19. Assessment of the NKp46 mRNA expression in different tissues and cell types unambiguously confirmed the strict NK cell specificity of the NKp46 molecule. Remarkably, in line with the ability of NKp46 to recognize ligand(s) on murine target cells, the cDNA encoding NKp46 was found to be homologous to a cDNA expressed in murine spleen. In conclusion, this study reports the first characterization of the molecular structure of a NK-specific receptor involved in the mechanism of NK cell activation during natural cytotoxicity.

Amino Acid Sequence↗
PubMed1998

Specific detection of a probiotic Lactobacillus strain in faecal samples by using multiplex PCR.

Lactobacillus gasseri 4B2 is a human isolate characterised by a strong autoaggregating phenotype mediated by APF (aggregation-promoting factor), a secreted protein. Two primer pairs were developed for simultaneous amplification of a specific fragment of the APF gene and a highly conserved region of the 16S rRNA gene. The specificity of this protocol was checked in DNA samples isolated from single and mixed cultures of Lactobacillus. The same amplification protocol was successfully used directly adding whole bacterial cells to PCR reaction tubes. The suitability of this method for in vivo studies was investigated through feeding L. gasseri 4B2 to mice and analysing colony forming units obtained by plating faecal samples on selective medium. The methodology allows a fast and reliable identification of the target strain without any DNA extraction procedure.

Animals↗
PubMed1998

Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy.

Inhibition of cerebral amyloid beta-protein deposition seems to be an important target for Alzheimer's disease therapy. Amyloidogenesis could be inhibited by short synthetic peptides designed as beta-sheet breakers. Here we demonstrate a 5-residue peptide that inhibits amyloid beta-protein fibrillogenesis, disassembles preformed fibrils in vitro and prevents neuronal death induced by fibrils in cell culture. In addition, the beta-sheet breaker peptide significantly reduces amyloid beta-protein deposition in vivo and completely blocks the formation of amyloid fibrils in a rat brain model of amyloidosis. These findings may provide the basis for a new therapeutic approach to prevent amyloidosis in Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Development and application of an in vitro methodology to determine the transit tolerance of potentially probiotic Lactobacillus and Bifidobacterium species in the upper human gastrointestinal tract.

An in vitro methodology which mimics in vivo human upper gastrointestinal transit was developed. The transit tolerance of potentially probiotic Lactobacillus and Bifidobacterium species was determined by exposing washed cell suspensions at 37 degrees C to a simulated gastric juice (pH 2.0), containing pepsin (0.3% w/v) and sodium chloride (0.5% w/v), and a simulated small intestinal juice (pH 8.0), containing pancreatin USP (1 g l-1) and sodium chloride (5 g l-1), and monitoring changes in total viable count periodically. The methodology was also employed to determine the effect of adding milk proteins (1 g l-1), hog gastric mucin (1 g l-1) and soyabean trypsinchymotrypsin inhibitor [SBTCI] (1 g l-1) on transit tolerance. The majority (14 of 15) of isolates lost > 90% viability during simulated gastric transit. Only one isolate, Lactobacillus fermentum KLD, was considered intrinsically resistant. The addition of milk proteins, singly and in combination, generally improved gastric transit tolerance. In this regard, two isolates, Lact. casei 212.3 and Bifidobacterium infantis 25962, exhibited 100% gastric transit tolerance in the presence of milk proteins. In general, the addition of hog gastric mucin did not influence simulated gastric transit tolerance of lactobacilli but tended to increase that of bifidobacteria. However, it increased that of Lact. casei 242 and Lact. salivarius 43338 but diminished that of B. bifidum 2715 and B. animalis Bo. Selected bile salts-resistant isolates were intrinsically tolerant to simulated small intestinal transit. Only Lact. casei F19 and B. adolescentis 15703T showed significant reduction in viability after 240 min. In general, the addition of milk proteins and SBTCI did not affect simulated small intestinal transit tolerance. However, they significantly improved the intrinsic resistance of Lact. casei F19 but diminished that of B. breve 15700T. It is concluded that, whereas the majority of bile salts-resistant lactobacilli and bifidobacteria may be intrinsically sensitive to gastric transit, they are intrinsically resistant to small intestinal transit. In addition, it is postulated that milk proteins and mucin may function as both buffering agents and inhibitors of digestive protease activity in vivo, thereby protecting ingested bacterial strains during upper gastrointestinal transit.

Adult↗
PubMed1998

Antibiotic susceptibility of potentially probiotic Bifidobacterium isolates from the human gastrointestinal tract.

Sixteen Bifidobacterium isolates from the human gastrointestinal tract were assayed for susceptibility to 44 antibiotics by soft agar overlay disc diffusion on TPY agar. Five isolates (3/7 B. bifidum and 2/3 B. breve) exhibited atypical antibiotic susceptibility profiles. Poor growth in the agar overlay accounted for susceptibility of B. bifidum but not B. breve isolates. All other isolates were resistant to cefoxitin (30 micrograms), aztreonam (30 micrograms), vancomycin (30 micrograms), amikacin (30 micrograms), gentamicin (10 micrograms), kanamycin (30 micrograms), streptomycin (10 micrograms), fusidic acid (10 micrograms), trimethoprim (5 micrograms), norfloxacin (10 micrograms), nalidixic acid (30 micrograms), metronidazole (5 micrograms), polymyxin B (300 micrograms) and colistin sulphate (10 micrograms), and they were susceptible to the six penicillins studied, cephalothin (30 micrograms), cefuroxime (30 micrograms), cefaclor (30 micrograms), ceftizoxime (30 micrograms), cefotaxime (30 micrograms), bacitracin (10 micrograms), chloramphenicol (30 micrograms), erythromycin (15 micrograms), clindamycin (2 micrograms), rifampicin (5 micrograms) and nitrofurantoin (300 micrograms). In addition, they varied in their susceptibility to cephradine (30 micrograms), cephazolin (30 micrograms), cefoperazone (75 micrograms), ceftriaxone (30 micrograms), ofloxacin (5 micrograms) and furazolidone (15 micrograms). They were resistant, or only marginally moderately susceptible, to ceftazidime (30 micrograms), netilmicin (10 micrograms), sulphamethoxazole (100 micrograms), cotrimoxazole (25 micrograms) and ciprofloxacin (5 micrograms), and susceptible or marginally moderately susceptible to tetracycline (30 micrograms). All B. bifidum isolates were susceptible to cefixime (5 micrograms). Four microorganism-drug combinations were evaluated for beta-lactamase activity but its absence suggested that cell wall impermeability was responsible for cephalosporin resistance among bifidobacteria. The antibiotic susceptibility of B. animalis 25527T was similar to that of the human isolates.

Anti-Bacterial Agents↗
PubMed1998

Presenilin 1 Met146Leu variant due to an A --> T transversion in an early-onset familial Alzheimer's disease pedigree from Argentina.

Most of the cases of early-onset familial Alzheimer's disease (FAD) are related to missense mutations in the presenilin 1 (PS-1) gene on chromosome 14. Although PS-1 mutations are distributed throughout the entire open reading frame, most mutations are found in transmembrane region II and hydrophilic loop VI encoded by exons 5 and 8, respectively. These two groups of substitutions are associated with an age of onset of 40-43 years for exon 5 and 45-55 years for exon 8, respectively. We have previously described a South American pedigree from Argentina with early-onset FAD (mean age of onset 38.9 +/- 3.9 years) with no mutations in exons 16 and 17 of the beta-protein precursor gene (betaPP770 transcript). Here we report the identification of an A --> T transversion at the first position of codon 146 of PS-1 in these patients. This missense mutation results in a Met --> Leu substitution, as reported for the Italian pedigrees Tor1.1 and FAD4. The significant differences in ages of onset and death among members of generations II-III and IV suggest that other genetic and/or environmental factors may influence disease phenotype in this pedigree.

Adenine↗
PubMed1998

A 70-kilodalton recombinant heat shock protein of Candida albicans is highly immunogenic and enhances systemic murine candidiasis.

The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immunogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis. The whole protein and its two fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects. Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-gamma), IL-12, and IL-10 but not IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-gamma was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-gamma upon in vitro stimulation of CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae. Their enhanced susceptibility was attributable to the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise either Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.

Animals↗
PubMed1998

Antibiotic susceptibility of potentially probiotic Lactobacillus species.

In recent years, the time-honored reputation of lactobacilli as promoters of gastrointestinal and female urogenital health has been qualified. This has occurred due to a rare association with human infection in the presence of certain predisposing factors and their potential to act as a source of undesirable antibiotic resistance determinants to other members of the indigenous microbiota. This necessitates greater caution in their selection for use in microbial adjunct nutrition and disease management (prophylaxis and therapy). It was against this background that 46 Lactobacillus strains from human and dairy sources were assayed for susceptibility to 44 antibiotics. All strains were resistant to a group of 14 antibiotics, which included inhibitors of cell wall synthesis (cefoxitin [30 microg] and aztreonam [30 microg]), protein synthesis (amikacin [30 microg], gentamicin [10 microg], kanamycin [30 microg], and streptomycin [10 microg]), nucleic acid synthesis (norfloxacin [10 microg], nalidixic acid [30 microg], sulphamethoxazole [100 microg], trimethoprim [5 microg], co-trimoxazole [25 microg], and metronidazole [5 microg]), and cytoplasmic membrane function (polymyxin B [300 microg] and colistin sulphate [10 microg]). All strains were susceptible to tetracycline (30 microg), chloramphenicol (30 microg), and rifampicin (5 microg). Four human strains and one dairy strain exhibited atypical resistance to a penicillin, bacitracin (10 microg), and/or nitrofurantoin (300 microg). One human strain was also resistant to erythromycin (15 microg) and clindamycin (2 microg). These resistances may have been acquired due to antibiotic exposure in vivo, but conclusive evidence is lacking in this regard. Seven microorganism-drug combinations were evaluated for beta-lactamase activity using synergy and nitrocefin tests. The absence of activity suggested that cell wall impermeability appeared responsible for beta-lactam resistance. The occurrence of a minority of lactobacilli with undesirable, atypical resistance to certain antibiotics demonstrates that not all strains are suitable for use as probiotics or bacteriotherapeutic agents. The natural resistance of lactobacilli to a wide range of clinically important antibiotics may enable the development of antibiotic/probiotic combination therapies for such conditions as diarrhea, female urogenital tract infection, and infective endocarditis.

Anti-Bacterial Agents↗
PubMed1998

Detection of bovine mitochondrial DNA in ruminant feeds: a molecular approach to test for the presence of bovine-derived materials.

A ban on ruminant-derived proteins in ruminant feeds has been introduced as a preventive measure to avoid the spread of bovine spongiform encephalopathy (BSE), as well as to minimize any potential risk of BSE transmission from bovines to humans. In the absence of commercially available efficient methods for identification of bovine-derived proteins in animal feeds, we developed a rapid and sensitive polymerase chain reaction (PCR)-based assay which allows detection and identification of a bovine-specific mitochondrial DNA sequence from feedstuffs. The amplified product encodes for the whole ATPase subunit 8 and the amino-terminal portion of the ATPase subunit 6 proteins, which are known to exhibit a relatively low degree of conservation among vertebrates. The specific amplification of such a bovine mitochondrial sequence from reference feedstuff samples was demonstrated by means of both direct sequencing and single-strand conformational analysis of the PCR product. Specificity was also confirmed by the absence of detectable homologous PCR product when using reference feedstuff samples lacking bovine-derived meat and bonemeals, or genomic DNA samples from vertebrates whose offals are commonly included in animal feeds. This method allows detection of the presence of bovine mitochondrial DNA in feedstuffs containing less than 0.125% of bovine-derived meat and bonemeals. Furthermore, it does not appear to be considerably affected by prolonged heat treatment. DpnII and SspI restriction endonuclease digestions of the unpurified PCR product may be used routinely to confirm the bovine origin of the amplified sequence. Since this method is specific, rapid, and sensitive, it could be successfully utilized as a routine control assay to evaluate the presence of bovine-derived meat and bonemeals in ruminant feeds.

Adenosine Triphosphatases↗
PubMed1997

p46, a novel natural killer cell-specific surface molecule that mediates cell activation.

Limited information is available on the surface molecules that are involved in natural killer (NK) cell triggering. In this study, we selected the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. BAB281 identified a novel NK cell-specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. Importantly, unlike the NK cell antigens identified so far, the expression of p46 was strictly confined to NK cells. Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. The p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A. Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex-restricted cytolysis mediated by human NK cells.

Amidohydrolases↗
PubMed1997

Selective detection, enumeration and identification of potentially probiotic Lactobacillus and Bifidobacterium species in mixed bacterial populations.

Lactobacillus and Bifidobacterium species constitute a significant proportion of probiotic cultures used in developed countries in 'microbial adjunct nutrition'. A number of differential plating methodologies have been developed which seek to selectively detect and enumerate these bacterial groups in bioproducts. Differences in oxygen tolerance, nutritional requirements, antibiotic susceptibility, and colony morphology and colour constitute the bases of differentiation in these methods. The choice of methodology depends on the nature of the bioproduct to be examined (wet or dry) and the presence of other bacteria such as starter cultures. In addition, a number of nucleic acid methods have been developed in recent years which enable the specific detection of these bacterial groups at species, subspecies and strain level in mixed populations. The methods use synthetic 16S and 23S rRNA-targeted hybridisation probes, the specificity of which can be adjusted to fit any taxonomic ranking from genus to genotype, for detection, enumeration and identification in situ or after differential plating. The combined use of differential plating and molecular strain typing methodologies provides food and medical microbiologists with a powerful and targeted approach to the detection, enumeration and identification of these bacterial groups and their members in a wide range of food and biological materials. An overview of these methods is presented in this review.

Bifidobacterium↗
PubMed1997

bcl-2 expression in pleural and extrapleural solitary fibrous tumours.

This study evaluated the immunoreactivity for bcl-2, a molecule involved in the control of programmed cell death, in cases of pleural (14) and extrapleural (2) solitary fibrous tumour (SFT), malignant mesotheliomas of different histological types, and a variety of extrapleural CD34-positive and CD34-negative spindle-cell tumours. In all SFTs, strong and diffuse immunostaining was demonstrated with anti-bel-2 antibody, sharply contrasting with the complete lack of staining observed in all mesotheliomas. The specificity of immunodetection of bcl-2 in SFT was confirmed by immunoblot analysis, showing a band consistent with the bcl-2 protein. At extrapleural locations, strong bcl-2 immunoreactivity was observed in Schwannoma (2/3 cases), synovial sarcoma (4/4 cases), and all cases of CD34-positive gastrointestinal stromal tumour (GIST; 10/10 cases). Most sarcomas were bcl-2-negative. Lack of bcl-2 expression was demonstrated in tumours which can pose problems in the differential diagnosis of SFT and can exhibit haemangiopericytoma-like features, including haemangiopericytoma (3 cases), dermatofibrosarcoma protuberans (16 cases), and deep-seated fibrous histiocytoma (3 cases). The constitutive expression of bcl-2 in SFT widens the spectrum of available markers for these tumours, providing a useful adjunct to their differential diagnosis in difficult cases at pleural and extrapleural sites, and contributing to the understanding of their histogenesis and molecular pathogenesis.

Adult↗
PubMed1997

Transient global brain hypoxia-ischemia in adult rats: neuronal damage, glial proliferation, and alterations in inositol phospholipid hydrolysis.

A model of ischemic-hypoxic brain injury which combines bilateral occlusion of common carotid arteries for 10 min and mild hypoxia (15% O2 for 10 min before and during occlusion) was developed. Global ischemia was assessed by a simplified EEG recording indicating isoelectric line, i.e. full arrest of cortical electrical activity. Histological examination of brain 7 days after ischemic insult showed from moderate to severe damage, mainly in the cerebral cortex (layers III, V and VI) and hippocampus (mainly CA1 subfield). The injury consisted of neuronal degeneration and necrosis with nuclear pyknosis and karyorrhexis. Immunohistochemical staining for gliofibrillar acidic protein showed a marked glial proliferation in the cerebral cortex and hippocampus. In the cortical slices, inositol phosphates accumulation stimulated by excitatory amino acid agonists (ACPD, ibotenate and quisqualate), as well as by norepinephrine and carbachol, was enhanced significantly (p < 0.01) with respect to sham-operated rats 7 days, but not 24 h, after the ischemic insult. The overall data show that the relatively simple transient brain hypoxia/ischemia rat model produces full arrest of cortical EEG, histopathological alterations and those relative to post-receptor neurochemical mechanisms characteristic of four-vessel occlusion model.

Animals↗
PubMed1997

Functions of S-layers.

Although S-layers are being increasingly identified on Bacteria and Archaea, it is enigmatic that in most cases S-layer function continues to elude us. In a few instances, S-layers have been shown to be virulence factors on pathogens (e.g. Campylobacter fetus ssp. fetus and Aeromonas salmonicida), protective against Bdellovibrio, a depository for surface-exposed enzymes (e.g. Bacillus stearothermophilus), shape-determining agents (e.g. Thermoproteus tenax) and nucleation factors for fine-grain mineral development (e.g. Synechococcus GL 24). Yet, for the vast majority of S-layered bacteria, the natural function of these crystalline arrays continues to be evasive. The following review up-dates the functional basis of S-layers and describes such diverse topics as the effect of S-layers on the Gram stain, bacteriophage adsorption in lactobacilli, phagocytosis by human polymorphonuclear leukocytes, the adhesion of a high-molecular-mass amylase, outer membrane porosity, and the secretion of extracellular enzymes of Thermoanaerobacterium. In addition, the functional aspect of calcium on the Caulobacter S-layer is explained.

Abortion, Veterinary↗
PubMed1996

Cerebrovascular amyloidosis in squirrel monkeys and rhesus monkeys: apolipoprotein E genotype.

Some neuropathological changes characteristic of aging and Alzheimer's disease (AD) in humans are present also in senescent non-human primates. The human apoE4 allele is associated with an increased risk of developing late-onset familial and sporadic AD. We found that rhesus monkeys and three subspecies of squirrel monkeys are homozygous for apoE phenotype with arginine at positions 112 and 158 as in human apoE4. However, in both species threonine replaces arginine at position 61 of human apoE. It was previously shown that arginine 61 was critical in determining apoE4 lipoprotein distribution in humans.

Alzheimer Disease↗
PubMed1996

Expression of human NKRP1A by CD34+ immature thymocytes: NKRP1A-mediated regulation of proliferation and cytolytic activity.

In this study, we show that NKRP1A is expressed and functions on a subset of immature human thymocytes. We took advantage of the monoclonal antibody (mAb) 191B8 that was obtained by immunizing mice with cultured human thymocytes characterized by an immature surface phenotype [CD2- CD3- CD4- CD8- stem cell factor receptor (SCFR)+] and expressing cytoplasmic CD3 epsilon chain. The 191B8 antibody homogeneously reacted with the immunizing population but not with most unfractionated thymocytes. It stained a minor population of resting immature thymocytes co-expressing CD34, SCFR, or both. Following culture of the CD34+ or CD34- fractions of CD2- CD3- CD4- CD8- purified immature thymocytes with recombinant interleukin-2 (rIL-2), the 191B8-defined antigen was expressed on virtually all cells even when 191B8+ cells were removed from the starting population. On the other hand, no 191B8+ cells were detected in fresh or cultured thymocytes expressing a more mature phenotype. Biochemical analysis of 191B8 mAb-reactive molecules revealed, under non-reducing conditions, two bands displaying apparent molecular masses of 80 and 44 kDa and a single band of 44 kDa under reducing conditions. Digestion with proteases indicated that the 80-kDa form represented a homodimeric form of two 44-kDa molecules, while deglycosylation with N-glycanase suggested the existence of four N-glycosylation sites. Transfection of COS7 or NIH3T3 cells with hNKRP1A cDNA showed that the 191B8 mAb recognized NKRP1A as shown by both immunofluorescence analysis and immunoprecipitation experiments. Functional studies showed that the 191B8/NKRP1A molecule mediated strong inhibition of the cytolytic activity of cultured CD2- CD3- immature thymocytes against a panel of tumor target cells. More importantly, 191B8 mAb induced proliferation of CD2- CD3- fresh thymocytes which was not increased by rIL-2. Thus, we propose that NKRP1A molecules, which are expressed in highly immature thymocytes, may play a regulatory role in their growth and function.

Antigens, CD34↗
PubMed1996

A novel surface molecule homologous to the p58/p50 family of receptors is selectively expressed on a subset of human natural killer cells and induces both triggering of cell functions and proliferation.

Human natural killer (NK) cells express inhibitory (p58) or activatory (p50) receptors for HLA-C alleles. Here, we describe a novel member of the p58/p50 family that is expressed by a subset of NK cells in about one third of donors. This molecule, termed p50.3, mediates NK cell triggering as revealed by the induction of intracellular free calcium mobilization, cytokine release and cytotoxicity. In addition, anti-p50.3 monoclonal antibody (mAb) induced a selective, strong proliferation of p50.3+ NK cells in peripheral blood lymphocytes. Although p50.3 molecules do not appear to display an obvious HLA class I specificity, they are usually coexpressed with known inhibitory receptors for HLA class I alleles, mAb-mediated cross-linking of these receptors leads to inhibition of the anti-p50.3 mAb-induced NK cell activation and proliferation. Surface p50.3 molecules are glycoproteins of approximately 55-58 kDa which, upon deglycosylation, display a relative molecular mass of 36 kDa, similar to that of deglycosylated (activatory) p50 receptors. Analysis of the two-dimensional peptide maps of the 50.3 molecules revealed a high homology with the other HLA-C-specific p58/p50 receptors. The use of a set of oligodeoxynucleotide primers, previously shown to amplify the activatory (p50) forms of HLA-C-specific receptors, consistently amplified in p50.3+ clones a cDNA sequence termed KKA3. This sequence belongs to the p58/p50 multigene family, that encodes for a transmembrane protein specifically stained by anti-p50.3 mAb in cell transfectants. Similar to p50 molecules, the KKA3-encoded molecules are characterized by two extracellular immunoglobulin-like domains, by the presence of a lysine in the transmembrane region and a short (39 amino acids) cytoplasmic tail which does not contain immune receptor tyrosine-based activation motifs (ITAM)-like sequences.

Amino Acid Sequence↗