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PubMed1999

Pars planitis: clinical features and class II HLA associations.

OBJECTIVE: To describe a cohort of patients with pars planitis followed at a single tertiary care institution, determine the frequency of multiple sclerosis and/or optic neuritis in patients with this disorder, and calculate gene frequencies of human leukocyte antigen (HLA) class II alleles in these patients. DESIGN: Fifty-three patients with the diagnosis of pars planitis underwent clinical record review or telephone interview for follow-up or both; 32 of these underwent phlebotomy for analysis of HLA class II alleles. MAIN OUTCOME MEASURES: Outcomes included visual acuity, occurrence of multiple sclerosis and/or optic neuritis, and HLA class II gene frequencies. RESULTS: With a mean follow-up of 2 years, approximately 90% of patients maintained a visual acuity better than 20/40 in at least one eye. The most frequently encountered ophthalmic complications included cystoid macular edema, cataract, and epiretinal membrane formation. Of 37 patients with pars planitis who had medical or neurologic follow-up evaluations, 6 (16.2%) developed multiple sclerosis. The HLA-DR15 allele, coding for one of the two HLA-DR2 subtypes, was associated with pars planitis (odds ratio = 2.86, 95% confidence interval = 1.42-5.78, P = 0.004). CONCLUSIONS: A common immunogenetic predisposition to multiple sclerosis and pars planitis may be associated with the HLA-DR15 allele. This association may represent genetic linkage to the HLA-DR locus or a role for the HLA-DR15 gene product in the pathogenesis of both of these diseases.

Adolescent↗
PubMed1997

HLA class II antigens and T lymphocytes in human nasal epithelial cells. Modulation of the HLA class II gene transcripts by gamma interferon.

BACKGROUND: Nasal polyps are characterized by a proliferation of the epithelial layer of the mucosa, cellular infiltrates and other pathological changes; however the mechanisms involved in polyp pathogenesis remain largely unclear. OBJECTIVES: We have taken two different approaches to study the cellular events involved in nasal polyposis. METHODS: First, through use of immunohistochemical methods, we have studied the expression of HLA class II antigens in epithelial cells of nasal polyps and the distribution of lymphocytes in the epithelium and in the subepithelial layer in patients with clinical conditions, such as asthma, atopy, aspirin intolerance or cystic fibrosis, and in subjects with an absence of concomitant diseases. Second, in order to investigate whether HLA class II expression is controlled at the pre- or post-transcriptional level, we studied the effect of interferon gamma (INF gamma) on epithelial cells in primary culture, which were derived from HLA class II negative and HLA class II positive nasal polyps. Total RNA was extracted from the cells and reverse-transcribed, and the c-DNA corresponding to DR, DP, DQ loci was amplified by PCR. RESULTS: Expression of HLA class II antigens by the epithelia of nasal polyps was more common in the presence rather than in the absence of concomitant asthma, atopy or cystic fibrosis (59% versus 40%). HLA-DR was the only HLA class II antigen expressed in the seven polyps taken from cystic fibrosis patients. The number of CD8+ cells was significantly higher in polyps associated with known clinical conditions and HLA class II antigen expression than it was in 'isolated' polyps and in HLA class II negative polyps. RNA transcripts for at least one or all three HLA-DR, DP and DQ antigens were detected in 10 cultures of the II HLA class II positive polyps. Conversely, 8 of 10 cultures derived from HLA class II negative polyps did not express HLA class II transcripts in the absence of INF gamma. Adding INF gamma (100 U/ml) to the latter cell cultures caused expression of transcripts of one or more HLA class II genes. CONCLUSIONS: We have shown that HLA class II antigens were more frequently detected in polyps of patients with an identified clinical syndrome than in those of asymptomatic subjects. Our results also suggest that IFN gamma regulates expression of HLA class II antigens in airway epithelial cells of the nasal polyps at the transcriptional level, and that cultured cells from nasal polyps represent a suitable model to investigate immune mechanisms involved in diseases such as atopy, asthma and cystic fibrosis.

CD4-CD8 Ratio↗
PubMed1996

Type III bare lymphocyte syndrome: lack of HLA class II gene expression and reduction in HLA class I gene expression.

The bare lymphocyte syndrome (BLS) consists of an association between a combined immunodeficiency disease and a significantly reduced expression of either human histocompatibility leukocyte antigens (HLA) class I (HLA-A, -B, -C) or HLA class II (HLA-DP, -DQ, -DR) at the cell surface. BLS type III, the more frequent form of this syndrome, is characterized by impaired expression of both class I and class II antigens on patients' cells, in particular on leukocytes. We describe herein the demonstration that expression of HLA class I molecules was reduced by approximately half on Epstein-Barr virus-transformed B cells (LCL) derived from type III BLS patients. HLA class I mRNA level was also decreased to the same extent. Expression of HLA class I molecules was also very significantly reduced at the surface of these fibroblasts as was mRNA specific for HLA class I. Simultaneously, the expression of HLA-DR molecules on LCL was even more greatly decreased, and the expression of HLA-DQ antigens was virtually abolished. Molecular analysis demonstrated an absence of mRNA for the alpha- and beta-chains of HLA-DQ and HLA-DR in the patients' lymphocytes. In general, such patients present with an association of an absence of expression of HLA class II antigens and a significantly reduced expression of HLA class I antigens. The mechanism of this association is still uncertain.

Child↗
PubMed1999

DNA typing of HLA class II genes (HLA-DR, -DQ and -DP) in Japanese patients with histiocytic necrotizing lymphadenitis (Kikuchi's disease).

The pathogenesis of histiocytic necrotizing lymphadenitis (HNL), which was reported first by Kikuchi et al. and Fujimoto et al. in 1972, is as yet unknown. HNL is frequently reported in Asian countries including Japan, however it is rare in Europe and North America. To elucidate whether the human leukocyte antigen (HLA) alleles and haplotypes are associated with HNL, we performed DNA typing of HLA class II genes (HLA-DR, -DQ, and -DP) in 86 patients with HNL and 525 unrelated healthy Japanese controls with polymerase chain reaction using sequence-specific oligonucleotide probes (PCR-SSOP). In this study, we found DPA1*01 and DPB1*0202 allele frequencies in HLA class II genes are significantly higher in HNL patients than in normal controls. It is known that the frequency of DPB1*0202 alleles is extremely low or absent in Caucasians (e.g., French 0.4%, Italian 0.8%) and Negroid (e.g., South African 0%, Hottentot 0%), but relatively frequent in Asians (e.g., Korean 9.9%, Japanese 4.5%). Previous reports have said the incidence of HNL is frequent in Asians but rare in other races. In light of this background, HLA class II genes of HNL and the incidence of HNL in Asian countries, including Japan, might have a positive relationship to DPA1*01 and DPB1*0202 allele.

Adolescent↗
PubMed2005

Ultrasensitive detection and phenotyping of CD4+ T cells with optimized HLA class II tetramer staining.

HLA class I tetramers have revolutionized the study of Ag-specific CD8+ T cell responses. Technical problems and the rarity of Ag-specific CD4+ Th cells have not allowed the potential of HLA class II tetramers to be fully realized. Here, we optimize HLA class II tetramer staining methods through the use of a comprehensive panel of HIV-, influenza-, CMV-, and tetanus toxoid-specific tetramers. We find rapid and efficient staining of DR1- and DR4-restricted CD4+ cell lines and clones and show that TCR internalization is not a requirement for immunological staining. We combine tetramer staining with magnetic bead enrichment to detect rare Ag-specific CD4+ T cells with frequencies as low as 1 in 250,000 (0.0004% of CD4+ cells) in human PBLs analyzed directly ex vivo. This ultrasensitive detection allowed phenotypic analysis of rare CD4+ T lymphocytes that had experienced diverse exposure to Ag during the course of viral infections. These cells would not be detectable with normal flow-cytometric techniques.

Amino Acid Sequence↗
PubMed1999

HLA class II genotype, HLA-DR B cell surface expression and allergen specific IgE production in atopic and non-atopic members of asthmatic family pedigrees.

HLA class II polymorphism is variably associated with sensitization to specific allergens, but few convincing HLA associations with asthma or the general state of atopy have been demonstrated. In this study we investigated HLA class II genotype associations with asthma, atopy and specific IgE (sIgE) production to six allergen extracts and six purified major allergens (Der p 1, Der p 2, Fel d 1, Can f 1, Alt a 1 and Phl p 5) in 176 individuals from 20 asthmatic family pedigrees. In selected individuals, cell surface HLA-DR peripheral B-cell expression was correlated with HLA-DRB1 genotype and atopic status. Results showed that HLA-DRB1*08 was negatively associated with asthma (2% vs 17%; Pc = 0.02; OR = 0.08) and atopy (0% vs 16%; Pc = 0.04; OR = 0.1), while DRB1*15 was positively associated with asthma (36% vs 13%; Pc = 0.02; OR = 3.6). Analysis of DRB1 sequences showed that only 29% of individuals with GAG TAC TCT ACG at codons 9-12 in one or both alleles were atopic, compared with 53% of individuals without this sequence (P = 0.002; OR = 0.36). DPA1*0201 was negatively associated with sIgE to both grass pollen mix and Phl p 5 (0% vs 23%; Pc = 0.02; OR = 0.14). A non-significant trend towards higher HLA-DR B-cell expression was seen in both non-atopic and DRB1*08 individuals. In conclusion, this single centre study has demonstrated a number of HLA class II genotype associations with asthma, atopy and sIgE to grass pollen mix and Phl p 5, including hitherto unreported DRB1*08, DRB1 codon 9-12 and DPA1*0201 associations. No significant associations between HLA-DR expression and DRB1 genotype or atopy were demonstrated, although a trend towards higher expression was seen in non-atopic individuals and individuals of DRB1*08 genotype.

Allergens↗
PubMed1999

Genetics and specific immune response in allergy to birch pollen and food: evidence of a strong, positive association between atopy and the HLA class II allele HLA-DR7.

BACKGROUND: In some geographic areas birch pollen represents the most prominent cause for airborne allergic diseases. Up to 70% of patients allergic to birch pollen are hypersensitive to fruits, especially apples. Associations have been found, in some instances, with a sensitivity to aeroallergens and HLA class II genes. OBJECTIVES: We investigated whether susceptibility or resistance to birch pollen allergy with and without food allergy was associated with HLA class II genes. METHODS: Blood samples were obtained from 2 groups of unrelated European-born white adults: 42 atopic patients (31 of them with asthma) and 42 healthy control subjects with no personal or familial history of asthma or atopy. Their antibody responses to birch pollen, apples, grass, and weed pollens were evaluated by skin tests, RASTs, and immunoprints. Genomic DNA was extracted from PBLs. The exons of DQA1, DQB1, DRB1, and DPB1 genes were selectively amplified by using the PCR method. Genotyping was carried out by digestion of the amplified DNA products with allele-specific endonucleases (PCR-RFLP), which recognize allelic variations in the polymorphic exon. RESULTS: We found no significant differences in the frequency of DPB1 alleles between patients and control subjects. HLA class II DR4 and/or DR7 alleles were present in 42.6% of the patients and in only 2.4% of the healthy subjects. These results confirm a previous study of a group of polysensitized atopic patients, which showed that DR4 and DR7 alleles were rare in healthy control subjects and frequently observed in atopic subjects with or without concomitant asthma. CONCLUSION: We conclude that the allele HLA-DR7 is significantly involved in the presentation of apple and pollen allergens. However, we suggest that this susceptibility is more related to atopy than to specific responses to allergens.

Adult↗
PubMed1995

HLA class II and HLA-B27 oligotyping in two Siberian native population groups.

It was the purpose of this study to better define the frequency of HLA-B27 subtypes and HLA class II alleles among indigenous populations from the eastern tip of the Chukotka Peninsula of Siberia, Russia, which have higher frequencies of HLA-B27 (40%) and spondyloarthropathies (2%) than Caucasian populations and test the hypothesis that these populations are more closely related to Orientals. Siberian Eskimos and Chukchi residing in four coastal villages on the Chukotka Peninsula inhabited by Siberian Eskimos and Chukchi people were examined using oligotyping of the polymerase-chain reaction-amplified second and third exons of the HLA-B27 gene. HLA-class II alleles (DRB1, DQA1 and DQB1) were similarly determined. Of 88 HLA-B27 positive individuals from these villages, all had HLA-B*2705, including the four patients with Reiter's syndrome and the five ankylosing spondylitis, except one Eskimo control who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. HLA-class II typing in 70 Siberian Eskimos and 71 Siberian coastal Chukchi revealed HLA-DRB1*0401, DRB1*0802, *0901 and *1402 to account for nearly all the DRB1 alleles found in this population, similar to what has been described in Eskimos in Alaska, but different from Chinese or native Americans in the U.S. The overwhelming majority of the individuals examined had HLA-DQB1*0301, similar to what has been observed in Native Americans. The Siberian Eskimos differed from the coastal Chukchi only in the occurrence of HLA-DRB1*0701, DQA1*0201, DQB1*0201 alleles, which occurred only in the former group. These data suggest that the Chukotka population is genetically more closely related to Caucasians and native Americans and less to other Oriental populations.

Base Sequence↗
PubMed1997

Neonatal lupus erythematosus: studies on HLA class II genes and autoantibody profiles in Japanese mothers.

Neonatal lupus erythematosus (NLE) is a rare disorder of neonates characterized by two major clinical manifestations: congenital heart block and cutaneous lupus lesions. The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. To clarify possible class II HLA associations with maternal autoantibody responses, haplotypic and allelic distributions, along with the polymorphism of the MHC class II HLA alleles, were analyzed based on PCR-RFLP results in 25 Japanese mothers of two groups defined by precipitating autoantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SSB antibodies, but not those with anti-Ro/SSA alone, the class II haplotypes DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*08032-DQA1*0103-DQB1*0601 as well as individual class II alleles DRB1*1101, DRB1*08032 and DQB1*0301 showed significantly increased frequencies compared to those in normal controls. All anti-Ro/SSA and anti-La/SSB positive mothers carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the DRB1 chain. These mothers also carried homozygous or heterozygous DQ6 and DQ3 alleles that shared the same amino acid residues at positions 27-36 and 71-77 of hypervariable regions of the DQB1 chain. Furthermore, all mothers with both anti-Ro/SSA and anti-La/SSB were homozygous for DPB1*0501. Nine of 10 anti-Ro/SSA and anti-La/SSB-positive mothers, but only 6 of 15 mothers with anti-Ro/SSA alone, had affected infants. Thus, our findings suggest that there may be immunogenetic differences among mothers according to their autoantibody profiles, and that mothers with both anti-Ro/SSA and anti-La/SSB are more likely to have infants with NLE than mothers with anti-Ro/SSA alone.

Animals↗
PubMed2005

Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G--possible implications for human reproduction and autoimmune disease.

A line of investigation indicates that one or several genes in the human major histocompatibility complex (MHC) influences reproductive success. Studies have revealed associations between human leukocyte antigen (HLA) class II genes and risk of recurrent spontaneous abortion (RSA) and pre-eclampsia. However, these genes are not expressed at the feto-maternal interface. Furthermore, associations between polymorphisms in the nonclassical HLA class Ib gene, HLA-G, and reproductive outcome have been demonstrated. HLA-G is expressed by extravillous trophoblast during pregnancy, making it a more obvious candidate gene for a possible influence on pregnancy outcome. HLA-G has immunomodulatory functions. We have studied linkage disequilibrium between HLA class II genes, primarily HLA-DRB1 alleles, and HLA-G alleles in women with RSA and their partners (n = 103) and in control women and their partners (n = 92). We found a significant linkage disequilibrium between HLA-DR3 and HLA-G*010102 in both the RSA and control populations. For all four studied HLA loci, the alleles in the haplotype HLA-DRB1*03.DQA1*05.DQB1*02.G*010102 was in clear linkage disequilibrium. This HLA haplotype has repeatedly been associated with different autoimmune diseases but also with RSA. The G*010102 allele includes a 14-bp sequence polymorphism in the 3' untranslated region of the gene, which has been associated with differences in HLA-G mRNA alternative splicing and stability. This 14-bp polymorphism has also been associated with RSA, pre-eclampsia, and outcome of in vitro fertilization. Implications of HLA polymorphism--and other polymorphic genes in the MHC for pregnancy outcome--and for autoimmune diseases during pregnancy are discussed.

Abortion, Habitual↗
PubMed2003

[Genetic history of Aleuts of the Komandor islands from results of analyzing variability of class II HLA genes].

Variability of the HLA class II genes (alleles of the DRB1, DQA1, and DQB1 loci) was investigated in a sample of Aleuts of the Commanders (n = 31), whose ancestors inhabited the Commander Islands for many thousand years. Among 19 haplotypes revealed in Aleuts of the Commanders, at most eight were inherited from the native inhabitants of the Commander Islands. Five of these haplotypes (DRB1*0401-DQA1*0301-DQB1*0301, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*0802-DQA1*0401-DQB1*0402, DRB1*1101-DQA1*0501-DQB1*0301, and DRB1*1201-DQA1*0501-DQB1*0301) were typical of Beringian Mongoloids, i.e., Coastal Chukchi and Koryaks, as well as Siberian and Alaskan Eskimos. Genetic contribution of the immigrants to the genetic pool of proper Aleuts constituted about 52%. Phylogenetic analysis based on Transberingian distribution of the DRB1 allele frequencies favored the hypothesis on the common origin of Paleo-Aleuts, Paleo-Eskimos, and the Indians from the northwestern North America, whose direct ancestors survived in Beringian/southwestern Alaskan coastal refugia during the late Ice Age.

Alleles↗
PubMed1996

Results of Expedicion Humana. II. Analysis of HLA class II alleles in three African American populations from Colombia using the PCR/SSOP: identification of a novel DQB1*02 (*0203) allele.

PCR/SSOP typing methods were used to analyze the HLA Class II DRB1, DQA1, DQB1 and DPB1 loci of samples from three African American populations of Colombia. Forty samples from the Cauca (Pacific), and twenty samples each from the Choco (North Pacific Coast) and the Providencia (Caribbean island) populations, were collected and the Class II loci analyzed under the auspices of the Expedicion Humana. Despite the limited number of samples analyzed, the African Colombian populations exhibit a very high degree of class II polymorphism. A great diversity of DRB1 alleles was found, with representatives from all serological classes, including 19 DRB1 alleles in the Providencia, 16 in the Cauca and 14 in the Choco groups. In addition, a novel DQB1*02 allele (*0203) was found in two individuals from the Cauca population of the Pacific Coast. The sequence of the DQB1*0203 allele, associated with DR3, differs from DQB1*0201 by only one nucleotide substitution (C-->A) in the second position of codon 57, resulting in an Ala to Asp change. The addition of DQB1*0203 brings the total number of DQB1 alleles identified to date to 26. HLA class II diversity is much greater in these African Colombian populations than that seen in nearby Amerindian populations. Analysis of regional Colombian African American HLA population genetics is discussed with respect to the Colombian Amerindian HLA genetics described in an accompanying paper.

Alleles↗
PubMed1998

[Primary immunologic deficiency by deficiency of HLA class II antigens: nine new Tunisian cases].

BACKGROUND: Bare lymphocyte syndrome is a rare inherited primary immunodeficiency. The majority of the patients reported to date are from North Africa. We report nine new Tunisian cases. POPULATION AND METHODS: Over a period of 5 years, we have established the diagnosis of bare lymphocyte syndrome in nine patients who belong to seven different families. Class II HLA antigen expression was studied on resting peripheral mononuclear cells and PHA blasts. RESULTS: The clinical symptoms started at the mean age of 4.5 months (2-10 months) with chronic diarrhea. The evolution was characterized by appearance of other recurrent infections: pneumopathies (seven cases), thrush (seven cases), otitis (five cases) and septicemia (four cases). Allergic manifestations were observed in four cases. Six patients died at the mean age of 30 months from severe denutrition. Class II HLA antigens were not expressed on resting and activated lymphocytes. The absolute count of TCD4+ lymphocytes was decreased in seven patients. Lymphoproliferative response to specific antigens was absent. Four patients had panhypogammaglobulinemia. CONCLUSION: This study confirms the frequency of this disease among the North African population. The severity of the recurrent infection suggests the diagnosis of bare lymphocyte syndrome. This disease is fatal in the absence of bone marrow transplantation.

Child, Preschool↗
PubMed1996

The studies of HLA class II (HLA-DR) system by PCR-SSO typing and the relationship with serological method.

By using two methods together, namely, the conventional serological typing and the new method which is oligonucleotide typing, in order to study the HLA system, it was concluded that the new method was better. Some subtypes were detectable from the new method, whereas, the serological typing yielded negative results such as DRB1 subtype "0103". This method, therefore, provided more information in order to study the HLA system. However, the new method was twice as expensive as the conventional serological method.

Adult↗
PubMed1993

Molecular mapping of the HLA class II region in HLA-DR3 associated idiopathic membranous nephropathy.

Susceptibility to IMN is associated, in European Caucasoids, with the extended HLA haplotype in A1, B8, and DR3. It is unclear from previous investigations of HLA class II genes whether the association with A1, B8, DR3 is due to an HLA-DR or -DQ locus, or both, or to another locus linked to HLA class II. To examine genetic polymorphism over a more extensive area of DNA than previously, we carried out long range mapping of the HLA class II region of A1, B8, DR3 patients and healthy controls to discover if new markers of disease could be identified at this level of organization. Large fragments of genomic DNA were cut using enzymes with infrequent restriction sites, and were separated by pulsed field gel electrophoresis (PFGE) and analyzed using a series of probes which cover the HLA class II region. In several different DR3 haplotypes examined, the overall content of DNA and organization of the class II region were similar. However, both patient and control B8, DR3 haplotypes contained an extra Pvul site in the DRB region, compared to the disease-neutral B18, DR3 haplotype. Further, the DP region of the patient B8, DR3 haplotypes contained an additional partial BssHII cutting site which was not identified in the control B8, DR3 haplotypes. This structural heterogeneity in the vicinity of DP could have implications for genetic susceptibility to IMN and for linkage disequilibrium.

Chromosomes, Human, Pair 6↗
PubMed1990

HLA class II genes: typing by DNA analysis.

A detailed understanding of the structure and function of the human major histocompatibility complex (MHC) has ensued from studies by molecular biologist during the last decade. Virtually all of the HLA genes have now been cloned, and the nucleotide sequences of their different allelic forms have been determined. Typing for these HLA alleles is a fundamental prerequisite for tissue matching in allogeneic organ transplantation. Until very recently, typing procedures have been dominated by serological and cellular methods. The availability of cloned DNA from HLA genes has now permitted the technique of restriction fragment length polymorphism (RFLP) analysis to be applied, with remarkable success and advantage, to phenotyping of both HLA Class I and Class II determinants. For the HLA Class II genes DR and DQ, a simple two-stage RFLP analysis permits the accurate identification of all specificities defined by serology, and of many which are defined by cellular typing. At the present time, however, RFLP typing of HLA Class I genes is not as practicable or as informative as that for HLA Class II genes. The present clinical applications of HLA-DR and DQ RFLP typing are predominantly in phenotyping of living donors, including selection of HLA-matched volunteer bone marrow donors, in allograft survival studies, and in studies of HLA Class II-associated diseases. However, the time taken to perform RFLP analysis precludes its use for the typing of cadaveric kidney donors. Nucleotide sequence data for the alleles of HLA Class II genes have now permitted the development of allele-specific oligonucleotide (ASO) typing, a second category of DNA analysis. This has been greatly facilitated by the ability to amplify specific HLA Class II DNA 'target' sequences using the polymerase chain reaction (PCR) technique. The accuracy of DNA typing techniques should ensure that this methodology will eventually replace conventional HLA phenotyping.

DNA↗
PubMed1997

Cytokine modulatable signalling through macrophage HLA class II. 1. IFN-gamma upregulates the efficiency of Ca2+ mobilization in response to ligation of macrophage HLA-DP.

The human macrophage line 2MAC, established recently from peripheral blood, expresses a number of lineage-specific markers as well as a broad array of intercellular adhesion molecules, including high levels of HLA class I and class II. We have presented evidence elsewhere that 2MAC can be productively applied to the study of signal transduction through macrophage HLA class II. Namely, we showed that ligation of 2MAC HLA class II, but not HLA class I, by monoclonal antibody (mAb) elicits an increase in free cytoplasmic Ca2+ concentration [Ca2+]i. Moreover, this Ca2+ flux appears to be functionally relevant: ligation of HLA-DR, but not HLA class I, by mAb results in the Ca2+ mobilization-dependent induction of tissue factor, the high-affinity cellular receptor for factor VII/VIIa. Here we show that 2MAC is uniquely valuable for addressing the efficiency of signal transduction through HLA class II. Namely, we show here that prior culture of 2MAC cells with interferon-gamma (IFN-gamma) profoundly upregulates subsequent Ca2+ mobilization in response to ligation of HLA-DP in the absence of increased cell surface HLA-DP expression. Because IFN-gamma has no effect on 2MAC HLA-DP expression, IFN-gamma must upregulate Ca2+ mobilization by increasing the efficiency of signal transduction through HLA class II (HLA-DP), by targeting some other component of the macrophage HLA class II signalling pathway.

Calcium↗