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PubMed1979

Immunoglobulin classes in skin basement membrane in systemic lupus erythematosus: clinical significance and comparison with classes of serum anti-DNA antibodies.

Biopsies of apparently normal skin were obtained from 30 unselected patients with systemic lupus erythematosus. The immunoglobulin class distribution of the immune deposits at the dermal-epidermal junction was determined in order to assess associated disease patterns and to investigate the possibility that the immunoglobulin classes in the skin were an indication of the classes of serum anti-native DNA antibodies. Biopsy specimens containing IgG deposits were obtained from 10 patients with more active disease and a greater incidence of glomerulonephritis than those patients with only IgM deposits or negative biopsies. However, in this unselected group of patients the immunoglobulin class of the immune deposits did not necessarily indicate the class of serum anti-native DNA antibodies. Therefore biopsy of clinically uninvolved skin will not always identify SLE patients with an immunological restriction to IgM antibody production.

Adult↗

PubMed2005

gon-14 functions with class B and class C synthetic multivulva genes to control larval growth in Caenorhabditis elegans.

Previous work showed that C. elegans gon-14 is required for gonadogenesis. Here we report that gon-14 encodes a protein with similarity to LIN-15B, a class B synMuv protein. An extensive region of GON-14 contains blocks of sequence similarity to transposases of the hAT superfamily, but key residues are not conserved, suggesting a distant relationship. GON-14 also contains a putative THAP DNA-binding domain. A rescuing gon-14::GON-14::VENUS reporter is broadly expressed during development and localizes to the nucleus. Strong loss-of-function and predicted null gon-14 alleles have pleiotropic defects, including multivulval (Muv) defects and temperature-sensitive larval arrest. Although the gon-14 Muv defect is not enhanced by synMuv mutations, gon-14 interacts genetically with class B and class C synMuv genes, including lin-35/Rb, let-418/Mi-2beta, and trr-1/TRRAP. The gon-14; synMuv double mutants arrest as larvae when grown under conditions supporting development to adulthood for the respective single mutants. The gon-14 larval arrest is suppressed by loss of mes-2/E(Z), mes-6/ESC, or mes-4, which encodes a SET domain protein. Additionally, gon-14 affects expression of pgl-1 and lag-2, two genes regulated by the synMuv genes. We suggest that gon-14 functions with class B and class C synMuv genes to promote larval growth, in part by antagonizing MES-2,3,6/ESC-E(z) and MES-4.

Alleles↗

PubMed2005

[Oral care delivery and top-class sports. Relationships according to dentists who are top-class sportsmen].

The aim of this qualitative study was to determine the opinions of eight top-class sports dentists, two women and six men, about the possible relationship between their performance of top-class sports and their oral care delivery as a general practitioner. Seven of the eight dentists interviewed, indicated a connection between their performance of top-class sports and their oral care delivery. In particular, it concerns aspects as working very disciplined and systemicly, the pursuit of perfection, having the capability to concentrate very much, and working with an achievement-oriented attitude, such as the repeated search for challenges and always being active in exercising. Furthermore, some dentists interviewed stated that in delivering oral care, on the one hand they are trying to back frontiers, and on the other hand they have experienced their limitations. In the discussion, the questions are pointed out how quality of oral care delivery can be assessed, if there is any top-class oral care, and if so, which the personal characteristics are of dentists delivering this top-class care.

Delivery of Health Care↗

PubMed1991

Random association between the peptide repertoire of A2.1 class I and several different DR class II molecules.

The interaction between synthetic peptides and A2.1 class I MHC molecules has been investigated using an inhibition of Ag presentation assay and unbiased peptide sets derived of either viral or eucaryotic origin. For the various sets, strong binding (defined as significant inhibition at the 30 micrograms/ml level) was detected in 7 to 46% of the peptides tested, with an overall frequency of 26%. A set of self-peptides derived from human beta 2 microglobulin was also included in the study. In this case, strong binding was detected in 3 of 15 peptides (20%), thus formally demonstrating a lack of self-/non-self-discrimination at the level of class I molecules. When the whole A2.1-binding database of 105 peptides thus generated was examined by sequence analysis, a significant correlation was found with a recently proposed A2.1-binding motif, whereas no particular positive or negative association was detected between the capacity to bind A2.1 and three different class II alleles (DR1, DR5, and DR7). Finally, using this approach, several peptides capable of binding both A2.1 and multiple DR alleles have been identified, suggesting possible candidates for development of peptide vaccines eliciting both class I and class II restricted responses.

Amino Acid Sequence↗

PubMed1984

The role of T cell subsets in the generation of secondary cytolytic responses in vitro against class I and class II major histocompatibility complex antigens.

Strain combinations generating cytotoxic T lymphocytes (CTL) specific for a single class I (K or D) or class II (A or E) MHC molecule were set up. The responder cells were separated into Ly subsets (Ly-1+2-, Ly-1-2+, and Ly-1+2+) on day 5 of culture by using lytic or non-lytic selection techniques and monoclonal Ly-specific antibodies. The separated subsets were restimulated on day 8 and tested for secondary CTL activity on day 12. Class II-specific secondary CTL could be generated from all three subsets, whereas class I-specific CTL developed only in the Ly-1+2+ and Ly-1-2+ subsets. The Ly-1+2+ cells underwent a phenotypic shift to Ly-1-2+ by day 12, whereas CTL generated from the Ly-1+2- and Ly-1-2+ subsets retained their phenotype up to the secondary effector stage. The cells separated according to their Ly phenotypes on day 5 were the progeny of unprimed progenitors expressing the same Ly phenotypes. Unprimed Ly-1+2+ cells gave rise to CTL in the absence of the other subsets, while unprimed Ly-1+2- and Ly-1-2+ cells required the help of Ly-1+2+ cells (or soluble factors) during priming to become non-lytic CTL precursors by day 5, and cytolytic cells after restimulation. The Ly-1+2- subset could generate class II-specific secondary CTL only in the absence of the other two subsets. Apparently, alloantigen-primed Ly-1+2+ and Ly-1-2+ cells suppressed the development of cytolytic activity in the Ly-1+2- subset. The combined data provide a comprehensive pathway of CTL differentiation from T cell subsets.

Animals↗

PubMed1995

A clinical evaluation of guided tissue regeneration in the treatment of class II and class III furcation bony defects.

This investigation was designed to compare the clinical efficacy of open flap/expanded polytetrafluoroethylene (e-PTFE) membrane combination therapy to open flap therapy alone in the treatment of class II and class III furcation bony defects. The efficacy was evaluated by statistical analysis of the change in values for probing pocket depth, gingival recession, and relative (probing) attachment level. The statistical analysis indicated that the guided tissue regeneration (GTR)-applied group had better efficacy than the non-applied group in the treatment of furcation bony defects. Moreover, the GTR-applied maxillary group had better efficacy than the GTR-applied mandibular group, and the GTR-applied class III group was better than the GTR-applied class II group. These results were diametrically opposed to the results from the non-applied class II group. These results were diametrically opposed to the results from the non-applied group. By histological examination, new attachment of newly formed cementum with inserting of oriented collagen fibers was noted. We also found new bone formation and partial bone repair in the former furcation bony defect.

Adult↗

PubMed2003

Analysis of part of the chicken Rfp-Y region reveals two novel lectin genes, the first complete genomic sequence of a class I alpha-chain gene, a truncated class II beta-chain gene, and a large CR1 repeat.

The Rfp-Y region lies on the same microchromosome as the B-F/B-L region of the B complex, yet in contrast to the latter it is poorly characterised. To date it has been shown to contain at least two class I alpha-chain ( Y-F) genes, a class II B-chain gene and a C-type lectin-like gene. We describe the sequencing and analysis of some 20 kb of the Rfp-Y region, and identify several new genes. These include two novel C-type lectin-like genes ( Y-Lec1 and Y-Lec2) that differ strongly from the previously described C-type lectin-like gene found in the Rfp-Y region. We describe a complete genomic sequence of a class I alpha-chain ( Y-F) gene and its promoter from the Rfp-Y region. The predicted cDNA from this gene has high homology to the previously reported Y-F cDNAs. The promoter contains an altered enhancer A element. This portion of the Rfp-Y region also contains a truncated class II B-chain ( Y-LB) gene, as well as a large chicken repeat 1 (CR1) element.

Amino Acid Sequence↗

PubMed1999

Characterization of MHC class I and beta(2)-microglobulin sequences in Atlantic cod reveals an unusually high number of expressed class I genes.

Degenerate polymerase chain reaction (PCR) primers based on conserved residues from alignments of species with already characterized major histocompatibility complex (MHC)-encoded sequences were used in the search for class I and beta(2)-microglobulin (b(2)m) genes in Atlantic cod (Gadus morhua L. ). After PCR amplification and subsequent sequencing a putative class I sequence was identified, from which a probe was designed and used to screen a spleen cDNA library from one single individual. The full-length clone obtained was sequenced and shown to be a classical Mhc class I-encoded sequence. It revealed the characteristic alpha1-, alpha2-, and alpha3-domains and transmembrane and cytoplasmic region, with several conserved amino acids. A PCR amplification from the alpha2-domain to the CY-region was performed on the same library, using a proof-reading enzyme. At least 11 unique additional sequences were isolated. Moreover, sequencing of the additional cDNA clones resulted in a total of 17 different Mhc class I sequences in this individual. A Southern hybridization of DNA from four different individuals using an alpha3-specific probe confirmed this large number of genes. Interestingly, based on differences mainly in their transmembrane region, the sequences obtained could be divided into two distinct groups. Within the groups no support could be obtained for any further subdivision. Southern experiments using an alpha1-specific probe gave almost the same restriction fragment length polymorphism with a high number of hybridizing bands, suggesting a low divergence in this part of the gene. Sequencing of PCR clones obtained with a proof-reading enzyme confirmed this at the nucleotide level. PCR amplification to isolate and characterize the b(2)m gene resulted in a sequence which was used to screen a thymus cDNA library. Two different alleles were obtained and these showed the characteristic features of known teleostean beta(2)m sequences. A Southern hybridization with genomic DNA from four different individuals suggested the presence of one b(2)m locus in Atlantic cod.

Amino Acid Sequence↗

PubMed2006

Heterogeneity of class I and class II MHC sequences in Schistosoma mansoni.

We investigated the genetic variations in class I and class II major histocompatibility complex (MHC) genes of Schistosoma mansoni and the effects of host MHC genotypes. S. mansoni was maintained in combinations of two mouse strains with different MHC genotypes, and the MHC gene sequences of the cercariae were investigated. The detected class I MHC gene sequences were variable, with high similarity between the H-2D(b) murine host and the parasite. For other combinations, however, the parasite sequence was homologous to those of anthropoids. All class II MHC sequences detected in S. mansoni were homologous to those of anthropoids. Our results suggest that the genetic variation in the MHC sequences of S. mansoni is derived in part from the current host, indicating horizontal transfer of the sequences from mammal to parasite.

Animals↗

PubMed1990

Differential expression of class I and class II major histocompatibility complex antigen in early postnatal rats.

Cells expressing major histocompatibility complex (MHC) antigens are rarely found in normal mature brains, but cells resembling microglia can be induced to express these antigens following the onset of neural degeneration. In young rats, these cells show spontaneous expression of class I MHC antigens, which is further enhanced in the superior colliculus by the degeneration resulting from eye removal. By contrast, class II MHC antigen expression does not occur spontaneously and can only be induced by eye removal when the lesion is performed after the first postnatal week, when the optic tract begins to myelinate. We suggest that different signals are responsible for induction of class I and of class II MHC antigen expression.

Animals↗

PubMedDate not supplied

MHC expression in nonlymphoid tissues of the developing embryo: strongest class I or class II expression in separate populations of potential antigen-presenting cells in the skin, lung, gut, and inter-organ connective tissue.

We define expression of major histocompatibility complex (MHC) antigens in the nonlymphoid tissues of the developing rat. Antibodies to class I heavy and light chains (b2-m), and to class II MHC proteins were used. Strongest MHC expression was by individual cells in the skin, lung, gut, and inter-organ connective tissue. The class I+ and class II+ cells were distinct populations, differing in morphology, distribution, and expression of macrophage-associated antigens. A nonimmunologic role for MHC proteins in development has been proposed. Yet the distributions and antigenic profiles lead us to emphasize immunologic functions that may be served by the early presence of MHC+ cells outside the forming lymphoid organs. Potential contributions to establishment of extrathymic or maternal/fetal tolerance are discussed. Localization of strongest MHC expression to individual connective tissue cells of the developing organs, rather than parenchymal cells, is of clinical relevance to transplantation of fetal tissue.

Animals↗

PubMed1995

Delivery of class I and class II MHC-restricted T-cell epitopes of listeriolysin of Listeria monocytogenes by attenuated Salmonella.

Using a Salmonella vaccine-Listeria infection model of intracellular infection, we studied the capacity of an attenuated strain of Salmonella carrying T-cell epitopes of listeriolysin (LLO) of L. monocytogenes to elicit epitope-specific T-cell responses. Class II (LLO 215-226) or class I (LLO 91-99) MHC-restricted T-cell epitopes of LLO were inserted within a central, hypervariable domain of the flagellin protein of an attenuated delta aroA Salmonella dublin strain. T cells from Listeria-immunized mice were activated by lysates or heat-killed preparations of Salmonella construct expressing the LLO 215-226 epitope, indicating that LLO 215-226 is processed and presented to T cells when offered to antigen-presenting cells as part of a flagellin-epitope fusion protein. The chimeric flagellin genes were integrated into the chromosome of the flagellin-negative S. dublin strain to obtain stable expression of the epitopes. Immunization with the living, chromosomally integrated Salmonella construct carrying LLO 215-226 epitope as part of the flagellin protein generated T cells reactive with the corresponding LLO peptide, indicating that this chimera can stimulate a class-specific immune response in vitro. The effect of flanking residues on the processing and presentation of MHC class I LLO 91-99 epitope was studied using Salmonella vaccine strains that express chimeric flagellins containing one of three LLO 91-99 inserts: 91-99 (normal flagellin amino acids as flanking residues); KK91-99KK (Lys-Lys flanking residues); and AAA91-99AAA (Ala-Ala-Ala flanking residues).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

Chemistry of peptides associated with MHC class I and class II molecules.

Recent developments have led to a clearer understanding of the association between peptides and MHC molecules. It is now clear that the peptides presented by MHC class I or class II molecules follow stringent rules that are different for each allelic product. The allele-specific interaction usually involves a sequence of nine amino acids spanning the MHC groove. For class I molecules, the entire peptide ligand is involved in allele-specific interaction with MHC but for class II, the peptides are longer and the nine amino acid sequence is roughly central to the peptide. Allele-specific interactions are brought about by anchoring peptide side chains in complementary pockets in the MHC groove. The sum of allele-specific peptide-MHC interaction requirements can be described as a motif, characterized by number, spacing and specificities of anchors, as well as the more degenerate preferences at non-anchor positions within the nonamer stretches. Such information is useful for T-cell epitope predictions.

Aged↗

PubMed2003

Mutation analysis of BrCA1, BrCA2, and p53 versus soluble HLA class I and class II in a case of familial endometriosis.

OBJECTIVE: To investigate possible correlation(s) between mutations of BrCA1, BrCA2, and p53 genes versus soluble HLA expression in familial endometriosis. DESIGN: Mutation analysis. SETTING: University teaching departments and hospital. PATIENT(S): A family with seven women in two generations with familial endometriosis. INTERVENTION(S): Mutation analysis of BrCA1, BrCA2, and p53 genes. MAIN OUTCOME MEASURE(S): A point mutation of the BrCA1 gene appears to inhibit soluble HLA secretion. RESULT(S): Among the three genes examined, only the BrCA1 gene showed a T to A mutation at position 3232 that correlates with total abolishment of both class I and class II antigen release. CONCLUSION(S): A possible correlation between a BrCA1 mutation and soluble HLA expression appears to exist. The mutation is not stage dependent and seemingly influences the secretion of both class I and class II antigens that are totally absent from the serum of only one family member.

Aged↗

PubMed1989

Class I and class II HLA antigen expression by transitional cell carcinoma of the bladder: correlation with T-cell infiltration and BCG treatment.

HLA class I and II glycoproteins from transitional cell carcinoma (TCC) and from perineoplastic and healthy vesical mucosa were characterized together with infiltrating cells by means of immunochemistry using specific monoclonal antibodies on frozen sections obtained during resection or radical cystectomy. Specimens were taken from 11 patients with TCC and five with healthy bladder mucosa. Four patients with TCC and four with healthy mucosa had been previously treated with a course of intravesical bacillus Calmette-Guerin (BCG). Ten out of 11 TCC samples expressed class I glycoproteins with a membrane pattern (diffuse in seven, focal in three) as normal epithelial cells from either controls or perineoplastic bladder. Interestingly, eight out of 11 TCC samples expressed class II antigens on their membrane that were also present in six cases in the perineoplastic tissue while the epithelial cells from four out of five normal bladders were completely negative. The epithelial display of class II antigens in the non-neoplastic areas and in the normal bladder correlates (p less than 0.001) with the degree of cellular infiltrate while such a relationship was not found between the HLA II expression of neoplastic cells and the infiltrate. BCG treatment was associated with a higher amount of inflammatory cells, prevalently T "activated" cells (CD5+,DR+), with a CD4/CD8 ratio always greater than 1. In the light of the role played by HLA glycoproteins in immune mechanisms, these results could help explain the positive action of BCG and the relative immunosensitivity of TCC.

Aged↗

PubMed1999

MHC class I- and class II-restricted processing and presentation of microencapsulated antigens.

Macrophages were found of having a strong capacity of phagocytosing small size microcapsules (MS) and presenting microencapsulated antigens to either CD4+ and CD8- T cells. The class I-restricted presentation of microencapsulated tetanus toxoid by macrophages requires an intracellular processing which might follow the phagosome-to-cytosol route to enter the classical MHC class I presentation pathway. In contrast, presentation of microencapsulated cytotoxic peptide PbCS252-260 to specific CD8+ T cells has been observed with different APC and is not blocked by cytochalasin D, suggesting that peptide released from MS may directly bind to MHC class I molecules on the cell surface. In the case of MHC class II-restricted T cells, prefixation or treatment of macrophages with chloroquine, brefeldin A and cycloheximide inhibits the presentation of microencapsulated and soluble tetanus toxoid. These findings illustrate the capacity of microencapsulated antigens to enter different presentation pathways and should facilitate the development of subunit vaccines.

Amino Acid Sequence↗

PubMed2001

HLA class I and class II allele and haplotype diversity in Martinicans.

The Martinican population is mainly the product of admixture between African people and French Caucasians. The aim of the present study is to investigate at the DNA level the polymorphism of HLA class I (HLA-A, HLA-B) and class II (HLA-DRB1, DQB1 and DPB1) genes in a population of 100 Martinicans. Allelic distributions and interlocus linkage disequilibria were compared to those observed in a French Caucasian population and in African or North American African populations. Our data revealed a higher degree of polymorphism in Martinicans than in Caucasians and showed a prominant contribution of African origin in the admixed genetic feature of this population. African characteristic alleles were significantly represented in Martinicans: A*30, *33 *34, *66, *74, *8001, B*1510, *35, *42, *53, DRB1*0302, *0804, *1202, *1304, *1503, DPB1*0101, *1701, *1801, *3901. Moreover a higher diversity of A*-B* and DRB1*-DQB1* associations was observed in Martinicans compared to Caucasians which also reflects the African genetic background of this population. In the whole, using PCR-based genotyping methods for HLA class I and class II loci, this study allows a preliminary description of HLA allele distribution in this Caribbean island and gives new elements which may be helpful in the anthropologic field as well as in HLA and disease association studies.

Africa↗

PubMed1995

Why do class I MHC molecules bind smaller peptides than class II MHC molecules?

This article attempts to assemble theoretical-teleological argument to explore possible answers to the question of why class I MHC molecules bind smaller peptides than class II MHC molecules and the associated question of why the size of peptides binding to class I molecules is approaching the limit of the self-non-self discrimination. I propose that the small size of most class I-binding peptides precludes the production of 'MHC-restricted' antibodies. Such a strategy avoids the possibility of antibodies binding to the epitopes recognized by CD8+ T cells, thus blocking effector function required for clearance of potentially lethal infections.

Animals↗