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PubMed1991

Organization of the fimbrial gene region of Bacteroides nodosus: class I and class II strains.

The fimbrial subunit genes of Bacteroides nodosus may be divided into two distinct classes, based on the sequence of the major subunit gene fimA (accompanying paper--Mattick et al., 1991). The genetic organization of the fibrial gene region in these two classes is also distinct. Upstream of fimA in both classes in opposite transcriptional orientation is the gene aroA which encodes amino acid biosynthetic enzyme 5-enolpyruvylshikimate-3-phosphate synthase. However, downstream of fimA the two classes are quite different until homology is restored at a bidirectional transcription termination signal separating the fimbrial operon from a gene clpB, which appears to encode the regulatory subunit of an ATP-dependent protease. Between aroA and clpB class I strains contain, apart from fimA, only one other gene (fimB). Sequence and polymerase chain reaction analyses indicate that fimB does not have a separate promoter but rather is co-transcribed with fimA at a level attenuated by the strength of the transcription termination signal in the intergenic region. In class II strains fimA is followed by a more extended region containing three genes, which appear to have the same transcriptional arrangement as fimB. The second of these genes (fimD) may represent a functional analogue of fimB although there is no close sequence homology. The first gene (fimC) has no obvious similarity to either fimB or fimD. Beyond fimD, at the 3' end of the class II-specific region, is a variant fimbrial subunit gene (fimZ) which is virtually identical in serogroups D and H and which appears to represent a duplicate, possibly redundant, gene closely related to the progenitor of the more divergent structural subunit fimA gene found in these strains. Comparisons of the predicted fimZ product with those of fimA in class I and class II strains, as well as of the boundaries of the class-specific regions, suggest that the class II sequences evolved in another type 4 fimbriate species and were subsequently substituted in the B. nodosus genome by lateral transfer. Analysis of the sequences flanking fimA in different strains indicates that recombinational exchange of both fimA and the entire operon has also occurred between strains, and is possibly a mechanism for disseminating structural diversity in the population.

Amino Acid Sequence↗

PubMed2003

Use of nucleotide analogs by class I and class II CCA-adding enzymes (tRNA nucleotidyltransferase): deciphering the basis for nucleotide selection.

We explored the specificity and nature of the nucleotide-binding pocket of the CCA-adding enzyme (tRNA nucleotidyltransferase) by using CTP and ATP analogs as substrates for a panel of class I and class II enzymes. Overall, class I and class II enzymes displayed remarkably similar substrate requirements, implying that the mechanism of CCA addition is conserved between enzyme classes despite the absence of obvious sequence homology outside the active site signature sequence. CTP substrates are more tolerant of base modifications than ATP substrates, but sugar modifications prevent incorporation of both CTP and ATP analogs by class I and class II enzymes. Use of CTP analogs (zebularine, pseudoisocytidine, 6-azacytidine, but not 6-azauridine) suggests that base modifications generally do not interfere with recognition or incorporation of CTP analogs by either class I or class II enzymes, and that UTP is excluded because N-3 is a positive determinant and/or O-4 is an antideterminant. Use of ATP analogs (N6-methyladenosine, diaminopurine, purine, 2-aminopurine, and 7-deaza-adenosine, but not guanosine, deoxyadenosine, 2'-O-methyladenosine, 2'-deoxy-2'-fluoroadenosine, or inosine) suggests that base modifications generally do not interfere with recognition or incorporation of ATP analogs by either class I or class II enzymes, and that GTP is excluded because N-1 is a positive determinant and/or the 2-amino and 6-keto groups are antideterminants. We also found that the 3'-terminal sequence of the growing tRNA substrate can affect the efficiency or specificity of subsequent nucleotide addition. Our data set should allow rigorous evaluation of structural hypotheses for nucleotide selection based on existing and future crystal structures.

Base Sequence↗

PubMed1985

The role of T8 in the cytotoxic activity of cloned cytotoxic T lymphocyte lines specific for class II and class I major histocompatibility complex antigens.

It is reported here that most cytotoxic T lymphocytes (CTL), which recognize class I major histocompatibility complex (MHC) loci, express the T cell differentiation antigen T8. However, a minority of T8+ CTL clones was found to recognize class II MHC antigens. To test the hypothesis that T8 is involved only in T cell recognition of class I MHC antigens, we studied the role of T8 in the cytotoxic activity of class II MHC-specific CTL. Monoclonal antibodies specific for T8 blocked the activity of most class I MHC-specific CTL clones but did not affect the activity of class II MHC-specific CTL clones. Moreover, a mild trypsin treatment of the clones, which removed and T8 determinant, affected the activity of class I MHC but not that of class II MHC-specific CTL clones. These findings indicate that the class II-specific MHC CTL clones described here did not require T8 for their cytolytic activity. The activity of one T8+ class I MHC-specific (HLA-B27) CTL clone (HG-61) against the B cell line JY, which was used to raise this CTL clone, was not blocked by trypsin treatment of this clone. However, the activity of CTL clone HG-61 against target cells different from JY but carrying the appropriate HLA specificity was blocked by anti-T8 antibodies and trypsin treatment. The implications of these findings for the hypothesis that T8 is involved only in the activity of CTL with a relatively low avidity for class I MHC antigens are discussed.

Antibodies, Monoclonal↗

PubMed1988

Amnion membrane epithelial cells express class I HLA and contain class I HLA mRNA.

Amnion epithelial cells in membranes from term deliveries, which have been reported not to express histocompatibility Ag, were evaluated for HLA by using an avidin-biotin immunoperoxidase staining system and for class I HLA mRNA by Northern blotting and in situ hybridization. There were three major findings from these studies. 1) Amnion cells frequently expressed class I HLA. Three mAb to monomorphic determinants of class I HLA were used: 61D2, PA2.6, and W6/32. 61D2 identified 1 of 8 fresh amnion membranes as class I positive whereas PA2.6 identified 4/8 and W6/32 identified 5/8. 2) Amnion cells contained class I HLA mRNA. RNA extracted from amnion membranes hybridized to a class I HLA probe (pHLA1.1) in Northern blotting. In situ hybridization procedures with pHLA1.1 showed that essentially all amnion cells contained class I HLA mRNA. 3) Levels of class I HLA mRNA in amnion cells could be modulated. Exposure of amnion explants to medium containing IFN-gamma enhanced levels of class I HLA mRNA in amnion cells, whereas epidermal growth factor diminished those levels. The results suggest that amnion cells transcribe class I HLA genes and are capable of synthesizing class I H chains but that expression may be modulated by extrinsic regulatory molecules.

Amnion↗

PubMed1993

Expression and modulation of class I and class II histocompatibility leukocyte antigens on human soft tissue sarcomas.

BACKGROUND: Class I and Class II histocompatibility leukocyte antigens (HLA) play an important role in the antigenic recognition and target cell killing by T-lymphocytes. Their expression and modulation with gamma interferon on human soft tissue sarcomas were investigated. METHODS: The phenotypic expressions of Class I and Class II HLA were determined by avidin-biotin immunoperoxidase staining using two monoclonal antibodies W6/32 and MEL3, respectively. RESULTS: The present study showed that soft tissue sarcomas frequently had demonstrable Class I HLA and less-frequently expressed Class II HLA: The staining for Class I HLA was more diffuse, and the staining for Class II HLA was generally patchy in appearance. The expressions of two antigens on cultured sarcoma cells were found in accordance with the findings of sarcoma tumors. The expression of Class I antigen was enhanced, and Class II was induced in two cell lines by gamma interferon. The in vitro modulation of HLA with gamma interferon was reversible. Gamma interferon at the testing dose did not have cytotoxic or antiproliferative effects on either cell lines. CONCLUSIONS: Through the modulation of HLA on soft tissue sarcomas, gamma interferon may play a role in the clinical management of sarcomas.

Cell Division↗

PubMed2004

Analysis of genomic and expressed major histocompatibility class Ia and class II genes in a hexaploid Lake Tana African 'large' barb individual (Barbus intermedius).

Expression of too many co-dominant major histocompatibility complex (MHC) alleles is thought to be detrimental to proper functioning of the immune system. Polyploidy of the genome will increase the number of expressed MHC genes unless they are prone to a silencing mechanism. In polyploid Xenopus species, the number of MHC class I and II genes has been physically reduced, as it does not increase with higher ploidy genomes. In the zebrafish some class II B loci have been silenced, as only two genomically bona fide loci, DAA/DAB and DEA/DEB, have been described. Earlier studies indicated a reduction in the number of genomic and expressed class II MHC genes in a hexaploid African 'large' barb. This prompted us to study the number of MHC genes present in the genome of an African 'large' barb individual (Barbus intermedius) in relation to those expressed, adopting the following strategy. Full-length cDNA sequences were generated from mRNA and compared with partial genomic class Ia and II sequences generated by PCR using the same primer set. In addition, we performed Southern hybridizations to obtain a verification of the number of class I and II B genes. Our study revealed three beta2-microglobulin, five class Ia, four class II A, and four class II B genes at the genomic level, which were shown to be expressed in the hexaploid barb individual. The class Ia and class II data indicate that the ploidy status does not correlate with the presence and expression of these MHC genes.

Amino Acid Sequence↗

PubMed1985

Effects of head position on intraoral pressures in Class I and Class II adults.

Variations in resting lip and tongue pressures and their relationship to alterations in head posture were investigated in subjects with Class I and Class II dental and skeletal morphology. Intraoral pressures were measured by means of transducers mounted in plastic carriers, customized for each subject from dental casts. Transducers were placed in the carriers to measure posterior lingual, anterior lingual, and labial pressures along the mandibular dentition. Ten Class I subjects and eleven Class II subjects participated. Pressures were recorded in natural head position, with 20 degrees of head extension and 20 degrees of head flexion. The Friedman two-way analysis of variance using ranked data was used to compare transducer location and head posture within skeletal classes. Anterior pressures were found to differ from posterior pressures in both classes. In Class I subjects, posterior lingual pressures were consistently different from labial pressures in all head positions. In Class II subjects, posterior lingual pressures differed from labial pressures in flexion and natural head positions, and from anterior lingual pressures in flexion and natural head positions. No increase in labial pressures with head extension was found in either Class I or Class II samples. Since every subject showed pressure changes with changes in head position, the influence of posture should be considered in studies on facial morphology and dental equilibrium.

Adolescent↗

PubMed2005

Influence of extraction and nonextraction orthodontic treatment in Japanese-Brazilians with class I and class II division 1 malocclusions.

BACKGROUND: The primary objective of this retrospective, longitudinal, cephalometric investigation was to study the influence of extraction and nonextraction orthodontic treatment on the facial height of Japanese-Brazilian children with Class I and Class II Division 1 malocclusions. METHODS: The sample included 59 mesocephalic patients distributed into 4 groups: group 1: Class I patients treated with 4 first premolar extractions; group 2: Class I patients treated nonextraction; group 3: Class II Division 1 patients treated with 4 first premolar extractions; group 4: Class II Division 1 patients treated nonextraction. The overall initial mean age of the groups was 12.14 years, and all groups were treated with standard edgewise appliances for a mean period of 2.49 years. The pretreatment and posttreatment stage comparison and the intergroup comparison of the treatment changes were conducted between extraction and nonextraction groups in the Class I and Class II malocclusion samples with t tests. RESULTS: The amounts of changes in the absolute magnitude of posterior and anterior facial heights and in the ratios of lower posterior facial height/lower anterior facial height and lower anterior facial height/total anterior facial height were similar between extraction and nonextraction treatment in both Class I and Class II malocclusions.

Analysis of Variance↗

PubMed1998

Simultaneous HLA Class I and Class II antibodies screening with flow cytometry.

A flow cytometric method of simultaneously screening both HLA Class I and Class II panel reactive antibodies (PRA) was developed using a pool of 30 different Class I and 30 different Class II microbeads coated with purified HLA antigens. The antibodies in the serum that react specifically to the coated HLA antigens are detected by using a FITC-conjugated antibody against human IgG. Percent PRA can be determined by the percentage of microbeads that react positively to the serum. There is no cross-reactivity between the Class I and Class II microbeads. A mixture of Class I and Class II microbeads can be distinguished by their different fluorescent properties on the flow cytometry analysis. Thus, both Class I and Class II PRA can be detected from a single tube reaction.

Antibodies↗

PubMed2002

Alterations of HLA class I and class II antigen expressions in borderline, invasive and metastatic ovarian cancers.

In an effort to understand whether HLA class I and II plays any role in the process of tumorigenesis and metastasis, we have immunohistochemically examined expression of HLA class I and II antigen by using the monoclonal antibodies (mAb) L368 (for beta2m of HLA class I), HC-10 (for HLA-B, C heavy chains), and LGII-612.14 (for HLA class II heavy chain) in 5 borderline serous malignancy (BSM), 20 serous adenocarcinomas (SA), 15 borderline mucinous malignancy (BMM), and 10 mucinous adenocarcinomas (MA) of human ovary tumor case tissues. In BSM, the distribution and intensity of HLA expressions failed to reach statistical significance. In SA, HLA class I beta2-microglobulin (beta2m), HLA-B, C heavy chains and HLA class II heavy chain antigen expressions were down-regulated. Although expressions of HLA-B, C heavy chains and class II heavy chain were down-regulated in metastatic SA, there were no differences in HLA expression levels between primary and metastatic lesions. In BMM, class II heavy chain expressions were down-regulated. In MA, beta2m, HLA-B, C heavy chains and class II heavy chain expressions were also down-regulated. Thus, we could distinguish the reduction or absence of HLA molecule expression was related to malignant potential. Loss of HLA class I and II molecules in invasive ovarian cancers raises the possibility that this could be a factor for tumor cells to retain invasiveness.

Adenocarcinoma↗

PubMed1998

Down-regulation of MHC class II molecules and inability to up-regulate class I molecules in murine macrophages after infection with Toxoplasma gondii.

Toxoplasma gondii is able to invade phagocytic cells of the monocyte-macrophage lineage and replicates within a parasitophorous vacuole. Since macrophages may activate specific T lymphocytes by presenting pathogen-derived antigens in association with molecules of the MHC, we investigated the in vitro expression of host cell molecules involved in antigen processing and presentation before and during infection of murine bone marrow-derived macrophages (BMM) with T. gondii. Fifty-one hours after addition of T. gondii tachyzoites at different parasite-to-host ratios, up-regulation of total MHC class II molecules by interferon-gamma (IFN-gamma) was dose-dependently abrogated in up to 50% of macrophages compared with uninfected control cultures. Quantitative analyses by flow cytometry revealed that the IFN-gamma-induced surface expression of class II antigens as well as the IFN-gamma-induced upregulation of class I molecules was significantly decreased in T. gondii-infected macrophage cultures compared with uninfected controls. However, the constitutive expression of MHC class I antigens was not altered after parasitic infection, and infected BMM remained clearly positive for these molecules. After infection of macrophages preactivated with IFN-gamma for 48 h, T. gondii also actively down-regulated an already established expression of MHC class II molecules. Furthermore, kinetic analysis revealed that the reduction in intracellular and plasma membrane-bound class II molecules started approximately 20 h after infection. While MHC class II antigens were most prominently reduced in parasite-positive host cells, culture supernatant from T. gondii-infected BMM cultures also significantly inhibited expression of these molecules in uninfected macrophages. However, down-regulation of MHC class II molecules was not mediated by an increased production of prostaglandin E2, IL-10, transforming growth factor-beta or nitric oxide by infected BMM compared with uninfected controls. Our data indicate that intracellular T. gondii interferes with the MHC class I and class II antigen presentation pathway of murine macrophages and this may be an important strategy for evasion from the host's immune response and for intracellular survival of the parasite.

Animals↗

PubMed1992

Altered binding of regulatory factors to HLA class I enhancer sequence in human tumor cell lines lacking class I antigen expression.

Class I antigens encoded in the major histocompatibility complex (MHC) (HLA in man, H-2 in the mouse) play a key role in the recognition of target cells by cytolytic T lymphocytes. Tumor cells frequently do not express class I MHC molecules, which strongly suggests that down-regulation of the latter facilitates escape of tumor cells from immune surveillance. The expression of class I MHC genes is tightly regulated. An enhancer element, conserved in the promoters of mouse and human MHC genes, has been shown to be important for mouse class I MHC gene expression. At least two related regulatory factors (KBF1 and NF-kappa B) bind to this regulatory element. We have analyzed the binding of these factors in cellular extracts of 23 human tumor cell lines displaying various levels of class I mRNA and surface expression. In this panel, combined deficiency of KBF1- and NF-kappa B-like DNA-binding activities was frequent among the class I-negative cell lines and correlated with the absence of class I mRNA. A few cell lines that lack KBF1 binding activity still display NF-kappa B-like activity and express normal levels of MHC class I mRNA. These results suggest (i) that, in the absence of KBF1, NF-kappa B or a related factor promotes MHC class I gene transcription; and (ii) that a combined defect in KBF1/NF-kappa B DNA-binding activity can cause a pleiotropic defect in class I gene expression, which may facilitate tumor progression.

Antibodies, Monoclonal↗

PubMed1997

Detection of HLA class I- and class II-specific antibodies by flow cytometry and PRA-STAT screening in renal transplant recipients.

BACKGROUND: Screening for HLA-specific antibodies has been performed by complement-dependent lymphocytotoxicity for many years. In recent years, methods involving the use of flow cytometry or ELISA have been developed. METHODS: This study has compared a flow cytometric screening technique for the detection of HLA class I- and class II-specific antibodies with a commercially available ELISA technique, PRA-STAT. RESULTS: A significant correlation was found between the two methods for the detection of antibodies in patients after transplantation (P<0.001). Specificity analysis confirmed that the PRA-STAT technique detected both HLA class I- and class II-specific antibodies. Screening of serum samples from patients who experienced graft loss by cytotoxic, flow cytometric, and PRA-STAT techniques showed that there was a significant correlation between all three methods for the detection of antibody, but that the best correlation for the panel-reactive antibody level was that between the flow cytometric and PRA-STAT techniques (r=0.86). This was principally due to the detection of both HLA class I- and class II-specific antibodies by these methods, whereas cytotoxic screening detected only class I-specific antibodies. CONCLUSIONS: These results suggest that PRA-STAT is a useful technique for the detection of both HLA class I- and class II-specific antibodies, rather than only class I-specific antibodies as previously described.

Antibodies↗

PubMed1999

Helicobacter pylori infection in immunized mice lacking major histocompatibility complex class I and class II functions.

The role of major histocompatibility complex (MHC) class I- and class II-restricted functions in Helicobacter pylori infection and immunity upon oral immunization was examined in vivo. Experimental challenge with H. pylori SS1 resulted in significantly greater (P </= 0.025) colonization of MHC class I and class II mutant mice than C57BL/6 wild-type mice. Oral immunization with H. pylori whole-cell lysates and cholera toxin adjuvant significantly reduced the magnitude of H. pylori infection in C57BL/6 wild-type (P = 0.0083) and MHC class I knockout mice (P = 0.0048), but it had no effect on the H. pylori infection level in MHC class II-deficient mice. Analysis of the anti-H. pylori antibody levels in serum showed a dominant serum immunoglobulin G1 (IgG1) response in immunized C57BL/6 wild-type and MHC class I mutant mice but no detectable serum IgG response in MHC class II knockout mice. Populations of T-cell-receptor (TCR) alphabeta+ CD4(+) CD54(+) cells localized to gastric tissue of immunized C57BL/6 wild-type and MHC class I knockout mice, but TCRalphabeta+ CD8(+) cells predominated in the gastric tissue of immunized MHC class II-deficient mice. These observations show that CD4(+) T cells engaged after mucosal immunization may be important for the generation of a protective anti-H. pylori immune response and that CD4(+) CD8(-) and CD4(-) CD8(+) T cells regulate the extent of H. pylori infection in vivo.

Administration, Oral↗

PubMed1993

Isolation of a classical MHC class I cDNA from an amphibian. Evidence for only one class I locus in the Xenopus MHC.

The amphibian Xenopus is an ectothermic vertebrate in which the MHC has been studied extensively at the functional, biochemical, and genetic levels. A cDNA clone corresponding to the MHC class la gene (Xela-UAA1f) of Xenopus laevis was isolated by screening a cDNA phage library with oligonucleotides based on NH2-terminal protein sequence. Three pieces of evidence support its status as a class la gene: 1) Previous biochemical data suggested that only one polymorphic class la molecule is expressed per MHC haplotype in X. laevis. NH2-terminal sequencing of the class I protein encoded by the f haplotype showed a single unambiguous sequence of the first 22 amino acids; the deduced protein sequence of the cDNA clone matches precisely to this peptide sequence; 2) Genes that hybridized to the cDNA clone segregated perfectly with the serologically typed MHC in two family studies; and 3) There is a strong conservation of amino acids in the peptide-binding region that have been shown in mammals to dock peptides at their NH2- and COOH-termini. In contrast to all other species that have been examined, there appears to be only one class I locus present in the MHC of X. laevis. Xenopus speciates by allopolyploidization, and there are Xenopus species with different levels of ploidy (2n-12n). Functionally, the MHC has been shown to be "diploidized" in most Xenopus species. As in previous studies with MHC class II and HSP70 probes, there is a trend toward maintaining a diploid number of class la genes in all Xenopus species regardless of their chromosome number, probably accomplished through a deletional mechanism. Thus, there is a strong pressure in Xenopus to maintain very few MHC-linked class I genes, exemplified both by the number of class I genes per MHC haplotype and by the number of class la genes per organism.

Amino Acid Sequence↗

PubMed1993

Protease treatment of nuclear extracts distinguishes between class II MHC X1 box DNA-binding proteins in wild-type and class II-deficient B cells.

The X box region is critical for directing the expression of class II major histocompatibility complex genes in B lymphocytes. Although several class II promoter-specific DNA binding factors have been described, only the X box region factor, RFX, shows a genetic correlation with class II expression, being deficient in some B cell lines derived from patients with class II-deficient congenital immunodeficiency. To further evaluate the role of X box DNA-binding proteins in class II gene expression, the role of the X box region was examined in both class II-positive and -negative lymphoid cells. In addition to the wild-type B cell line Raji, two class II transcriptional mutant cell lines, SJO and RJ2.2.5, and Jurkat, a class II negative T cell line, were examined. In contrast to wild-type B cells, neither of the class II mutant cell lines could use the X box region to direct the expression of a transiently transfected reporter gene, indicating that the X box-dependent transcriptional pathway is defective in these cells. The binding activity of the X1 box DNA-binding protein RFX was examined and found to be present in wild-type B cells and the mutant RJ2.2.5 but was absent in SJO and Jurkat. However, other X1 box-specific activities were detected in all these cell lines. To determine whether these different X1 box activities represented distinct DNA binding proteins or multimeric forms of the same factor(s), protease treatment of the crude nuclear extracts followed by DNA-binding assays were carried out and demonstrated that B cell extracts contain at least two X1-specific factors. One of these cleaved products (band 1 pk) correlates with RFX activity. A similar comparison with protease-treated extracts prepared from Jurkat cells demonstrated the presence of the band 1pk activity despite an absence of the native RFX activity. In contrast, protease treatment and analysis of SJO extracts showed no detectable levels of the band 1pk activity. These results demonstrate that multiple X1 box-specific DNA-binding activities exist in all lymphoid cells, but the presence of an actively binding RFX species correlates with class II transcription.

B-Lymphocytes↗

PubMed1996

The presentation of class I and class II epitopes of listeriolysin O is regulated by intracellular localization and by intercellular spread of Listeria monocytogenes.

The hemolysin, listeriolysin 0 (LLO), produced by Listeria monocytogenes is both a virulence factor and an immunodominant Ag. In this study, we investigated how the lytic activity of LLO effects the context of presentation of two known LLO epitopes by either class I or class II MHC molecules. T cell hybridomas were used to monitor each peptide/MHC ligand. APCs infected with strains of Listeria expressing hemolytic LLO strongly presented the class I MHC epitope; however, this ligand was not well presented by cells infected with nonhemolytic Listeria. In contrast, there was almost no presentation of the class II-binding LLO epitope in cells infected with fully hemolytic Listeria. Only hemolysin-deficient Listeria were presented by class II MHC. Listeria expressing wild-type LLO but deficient in other virulence factors showed a presentation pattern equivalent to that of hemolytic Listeria. To address further the divergence of presentation, we used an intercellular spread assay to detect Ag presentation by cells neighboring the primarily infected one. We found that hemolytic Listeria were presented by both class I and II MHC on cells adjacent to the initially infected one(s). Finally, our kinetic analysis of presentation revealed that the class II ligand is presented over 4 h before the class I ligand. We have demonstrated that LLO's lytic activity potentiates presentation of listerial Ags by class I MHC and inhibits presentation via class II MHC. LLO-mediated intracellular localization (cytoplasmic vs endosomal) of bacteria corresponds to the operative presentation pathway.

Animals↗

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↗