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PubMed1981

Sequence homology among different size classes of plant mtDNAs.

Supercoiled mtDNAs were isolated from tissue culture cells of tobacco, bean, and corn, and the smallest size classes were used to study the relationships among the different size classes of each species through restriction digests and hybridizations. Three of the smallest tobacco mtDNAs [10.1, 20.2, and 28.8 kilobases (kb)], the two smallest bean mtDNAs (1.9 and 3.8 kb), and the two smallest corn mtDNAs (1.5 and 1.8 kb) were extracted from the gels and nick translated. The 10.1-kb tobacco mtDNA hybridizes to all the other tobacco mtDNA size classes and a large percentage of the tobacco mtRNAs. Restriction digests indicate that the 20.2-kb size class is a dimer of the 10.1-kb size class. The 1.9-kb bean mtDNA hybridizes to all but three of the bean mtDNA size classes and hybridizes to two mtRNAs. Restriction digests indicate that the 3.8-kb size class is a dimer of the 1.9-kb size class. The 1.5- and 1.8-kb corn mtDNAs, which do not have any Hha I restriction fragments in common, both hybridize to many of the same size classes of the corn mtDNA profile and, in addition, each hybridizes to a few size classes not recognized by the other. The 1.5- and 1.8-kb size classes both hybridize to two RNAs, one of which they appear to have in common. However, with both the 1.9-kb bean mtDNA and the two corn mtDNAs, the molecular sizes of the two RNAs exceed those of the respective DNAs. The possible role and origin of the many size classes are discussed.

Journal Article↗

PubMed1995

Genomic structure and expression of the ADH7 gene encoding human class IV alcohol dehydrogenase, the form most efficient for retinol metabolism in vitro.

Human alcohol dehydrogenase (ADH) consists of a family of five evolutionarily related classes of enzymes that collectively function in the metabolism of a wide variety of alcohols including ethanol and retinol. Class IV ADH has been found to be the most active as a retinol dehydrogenase, thus it may participate in retinoic acid synthesis. The gene encoding class IV ADH (ADH7) has now been cloned and subjected to molecular examination. Southern blot analysis indicated that class IV ADH is encoded by a single unique gene and has no related pseudogenes. The class IV ADH gene is divided into nine exons, consistent with the highly conserved intron/exon structure of other mammalian ADH genes. The predicted amino acid sequence of the exon coding regions indicates that a protein of 373 amino acids, excluding the amino-terminal methionine, would be translated, sharing greater sequence identity with class I ADH (69%) than with classes II, III or V (59-61%). Expression of class IV ADH mRNA was detected in human stomach but not liver. This correlates with previous protein studies, which have indicated that class IV ADH is the major stomach ADH but unlike other ADHs is absent from liver. Primer extension studies using human stomach RNA were performed to identify the transcription initiation site lying 100 base pairs upstream of the ATG translation start codon. Nucleotide sequence analysis of the promoter region indicated the absence of a TATA box sequence often located about 25 base pairs upstream of the start site as well as the absence of GC boxes, which are quite often seen in promoters lacking a TATA box. The class IV ADH promoter thus differs from the other ADH promoters, which contain either a TATA box (classes I and II) or GC-boxes (class III), suggesting a fundamentally different form of transcriptional regulation.

Alcohol Dehydrogenase↗

PubMed2006

IgA class antibodies to 2-oxo-acid dehydrogenase complex are not predictive markers of histopathological progression in primary biliary cirrhosis.

Although antimitochondrial antibody (AMA) is the characteristic serological feature of primary biliary cirrhosis (PBC), its pathogenic role remains unclear. In our previous study, we reported a positive correlation between immunoglobulin (Ig) A class anti-2-oxo-acid dehydrogenase complex (2-OADC) and histopathological stage. To determine whether the appearance of IgA class anti-2-OADC by immunoblotting represents an early marker of more aggressive disease or whether it is late finding during the disease course of PBC, we tested not only the entire IgA class but also IgA1, IgA2 and secretory IgA class anti-2-OADC in serial serum samples from 15 patients with PBC. During the median observation period of 51 months, four cases showed histopathological progression (from stage 1 to 2, stage 1 to 3, stage 1 to 4 and stage 2 to 4). There was no statistically significant correlation between the above IgA class anti-2-OADCs and histopathological progression. There was no significant correlation between histopathological stages and IgA2 class anti-2-OADC or secretory IgA class anti-2-OADC by immunoblotting. IgA class anti-2-OADC was more frequent in stages 3-4 than in stages 1-2 (p = 0.0049), but IgA1 class anti-2-OADC was more frequent in stages 1-2 than in stages 3-4 (p = 0.0232). Our present study demonstrated that serum IgA class 2-OADC was not a predictive marker of histopathological progression but was associated with the histopathological stage of PBC. Although the IgA class AMA may have a specific pathogenic role for PBC, the discrepant results between IgA and IgA1 class anti-2-OADC should be further assessed to investigate different functional activities depending on their molecular form.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed1993

Alcohol dehydrogenases: gene multiplicity and differential functions of five classes of isozymes.

Mammalian alcohol dehydrogenases (ADHs) constitute an enzyme family of multiple forms (isozymes) which are differentially distributed throughout the body. Subunit types alpha, beta and gamma in dimeric combinations constitute the isozymes of human liver class I ADH, and are >94% homologous in structure. Human pi and chi subunits form homodimeric Class II and III ADH isozymes. pi-ADH is liver specific whereas chi-ADH is widely distributed throughout the body. A sixth human ADH subunit (designated mu or sigma), forming a new dimeric human stomach ADH, has been recently reported as Class IV ADH. Evidence for a seventh human ADH subunit has also been described, designated as Class V, the transcripts having been reported in the stomach and liver. All five classes of ADH represent isozymes which are homologous but exhibit at least 30% sequence differences in primary srtructure. Kinetic analyses of four of these classes of ADH indicated differential functions, serving either in the oxidative or reductive mode. Studies from various laboratories indicate the following respective functions: oxidation of aliphatic and aromatic alcohols-liver Class I and Class II, and stomach Class IV ADHs; reduction of peroxidic aldehydes-Classes I, II and IV; 'biogenic' alcohol oxidation-Classes I and II; and glutathione-dependent formaldehyde dehydrogenase-Class III.

Journal Article↗

PubMed1989

Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever.

The antigenic relatedness of surface-exposed portions of M protein molecules derived from group A streptococcal isolates representing more than 50 distinct serotypes was examined. The data indicate that the majority of serotypes fall into two major classes. Class I M protein molecules share a surface-exposed, antigenic domain comprising the C repeat region defined for M6 protein. The C repeat region of M6 protein is located adjacent to the COOH-terminal side of the pepsin-susceptible site. In contrast, Class I M proteins display considerably less antigenic relatedness to the B repeat region of M6 protein, which lies immediately NH2-terminal to the pepsin site. Surface-exposed portions of Class II M proteins lack antigenic epitopes that define the Class I molecules. Studies in the 1970s demonstrated that M protein serotypes can be divided into two groups based on both immunoreactivity directed to an unknown surface antigen (termed M-associated protein) and production of serum opacity factor. These two groups closely parallel our current definition of Class I and Class II serotypes. Both classes retain the antiphagocytic property characteristic of M protein, and Class II M proteins share some immunodeterminants with Class I M proteins, although the shared determinants do not appear to be exposed on the streptococcal surface. Nearly all streptococcal serotypes associated with outbreaks of acute rheumatic fever express M protein of a Class I serotype. Thus, the surface-exposed, conserved C repeat domain of Class I serotypes may be a virulence determinant for rheumatic fever.

Antigens, Bacterial↗

PubMed2003

SamCluster: an integrated scheme for automatic discovery of sample classes using gene expression profile.

MOTIVATION: Feature (gene) selection can dramatically improve the accuracy of gene expression profile based sample class prediction. Many statistical methods for feature (gene) selection such as stepwise optimization and Monte Carlo simulation have been developed for tissue sample classification. In contrast to class prediction, few statistical and computational methods for feature selection have been applied to clustering algorithms for pattern discovery. RESULTS: An integrated scheme and corresponding program SamCluster for automatic discovery of sample classes based on gene expression profile is presented in this report. The scheme incorporates the feature selection algorithms based on the calculation of CV (coefficient of variation) and t-test into hierarchical clustering and proceeds as follows. At first, the genes with their CV greater than the pre-specified threshold are selected for cluster analysis, which results in two putative sample classes. Then, significantly differentially expressed genes in the two putative sample classes with p-values < or = 0.01, 0.05, or 0.1 from t-test are selected for further cluster analysis. The above processes were iterated until the two stable sample classes were found. Finally, the consensus sample classes are constructed from the putative classes that are derived from the different CV thresholds, and the best putative sample classes that have the minimum distance between the consensus classes and the putative classes are identified. To evaluate the performance of the feature selection for cluster analysis, the proposed scheme was applied to four expression datasets COLON, LEUKEMIA72, LEUKEMIA38, and OVARIAN. The results show that there are only 5, 1, 0, and 0 samples that have been misclassified, respectively. We conclude that the proposed scheme, SamCluster, is an efficient method for discovery of sample classes using gene expression profile. AVAILABILITY: The related program SamCluster is available upon request or from the web page http://www.sph.uth.tmc.edu:8052/hgc/Downloads.asp.

Algorithms↗

PubMed2006

Diverse class 2 integrons in bacteria from beef cattle sources.

OBJECTIVES: The purpose of this study was to determine the diversity of class 2 integrons in bacteria isolated from beef cattle sources. METHODS: The variable regions of a subset of 11 class 2 integron-containing bacteria were analysed by PCR and DNA sequencing for the presence of novel rearrangements. RESULTS: A total of six different class 2 integron arrays were identified and four of these were fully characterized. Three of the four arrays characterized have been previously described; however the remaining array is unlike previously described class 2 integrons. The novel class 2 integron was found in Providencia stuartii and contains an apparently functional class 2 integrase. Examination of the variable region of the P. stuartii integron identified nine open reading frames, mostly of unknown function, and represents the first report of a class 2 integron without inserted antibiotic resistance gene cassettes. CONCLUSIONS: This study has identified a novel class 2 integron found in P. stuartii that contains an apparently functional naturally occurring class 2 integrase. Further investigation of this novel class 2 integron is required to determine the impact of a functional class 2 integrase upon the evolution of class 2 integrons.

Animals↗

PubMed1996

Major histocompatibility complex class I expression on neurons in subacute sclerosing panencephalitis and experimental subacute measles encephalitis.

Lack of major histocompatibility class I antigens on neurons has been implicated as a possible mechanism for viral persistence in the brain since these antigens are required for cytotoxic T-lymphocyte recognition of infected cells. In subacute sclerosing panencephalitis (SSPE), measles virus (MV) persists in neurons, resulting in a fatal chronic infection. MHC class I mRNA expression was examined in formalin-fixed brain tissue from 6 SSPE patients by in situ hybridization. In addition MHC class I protein expression in MV-infected neurons was examined in experimental Subacute Measles Encephalitis (SME) by double immunohistochemistry. MHC class I mRNA expression was found to be upregulated in SSPE tissues studied, and in 5 out of 6 cases the expression was definitively seen on neurons. The percentage of neurons expressing MHC class I mRNA ranged between 20 to 84% in infected areas. There was no correlation between the degree of infection and expression of MHC class I molecules on neurons. Importantly, the number of neurons co-expressing MHC class I and MV antigens was markedly low, varying between 2 to 8%. Similar results were obtained in SME where 20 to 30% of the neurons expressed MHC class I but <8% co-expressed MHC class I and MV antigens. Perivascular infiltrating cells in the infected regions in SME expressed IFNgamma immunoreactivity. The results suggest that MV may not be directly involved in the induction of MHC class I on neurons and that cytokines such as IFNgamma may play an important role. Furthermore, the paucity of neurons co-expressing MHC class I and MV antigens in SSPE and SME suggests that such cells are either rapidly cleared by cytotoxic T lymphocytes (CTL), or, alternatively, lack of co-expression of MHC class I on MV infected neurons favors MV persistence in these cells by escaping CTL recognition.

Adult↗

PubMed1985

Heterologous repressor-operator recognition among four classes of tetracycline resistance determinants.

Homologous and heterologous repressor-operator interactions among four different classes of tetracycline resistance determinants have been compared. These are represented by RP1/Tn1721 (class A), R222/Tn10 (class B), pSC101/pBR322 (class C), and RA1 (class D). By the use of the purified repressor proteins of class A (TetRA) and class B (TetRB), operator sequences of all four classes are recognized by both with an identical stoichiometry of four repressor subunits per control sequence, but with different affinities. In vitro transcription has been used to demonstrate regulatory activities of TetRA and TetRB upon all four classes of tet genes. Tetracycline acted as an inducer. A functional relationship among the tet regulatory systems was also shown in vivo by complementation of a class A tetR'-galK fusion mutant with the tetR genes of classes A, B, and C. Repression of tetRA-linked galactokinase was ca. 80% in the presence of tetRA or tetRC, and ca. 50% in the presence of tetRB. Taken together, these results demonstrate heterologous repressor-operator interaction, suggesting close relationships among the four classes of Tcr determinants.

Base Sequence↗

PubMed1982

Evidence for two classes of chromatin-associated Epstein-Barr virus-determined nuclear antigen.

A new class of Epstein-Barr virus nuclear antigen (EBNA) was identified by the complement fixation assay. This new species of EBNA is more tightly bound to chromatin and was termed class II EBNA, as opposed to the more weakly associated species, class I EBNA. Preparations of this new antigen(s) specifically reduced absorption with the titer of anti-EBNA antibodies as determined by the anticomplement immunofluorescence assay. Therefore, the complement fixation antigens (class II EBNA) appear to be related to the classical EBNA (class I EBNA). The class I EBNA was found to focus at the same pH (4.6) as the soluble antigen found in the cytosol. The class II EBNA differed from the class I EBNA with regard to its overall charge, molecular size, antigenicity, and affinity for chromatin. The class II EBNA appeared to be a basic protein, based on its apparent pI of 9.2 and its binding to cation-exchange resins. It differed from histones with regard to its molecular size (molecular weight between 60,000 and 70,000) and its elution from hydroxylapatite chromatography. Steps were taken to prevent proteolysis and artifacts in the immunological assays and in the overall charge estimation of the new antigen by nonspecific basic histone protein-acidic protein interactions. Both class I and class II EBNA were identified by radioimmunoelectrophoresis on two-dimensional polyacrylamide gels with pI values of 5.0 and 8.5, respectively, and a molecular weight range of 60,000 to 70,000 for both. A lower-molecular-weight antigen identified by molecular sieve chromatography appeared to be due to interference by histones in the immunoassays since it was not observed by the two-dimensional gel electrophoresis. Further characterization of this class II EBNA is in progress.

Antigens, Viral↗

PubMed2003

Mutational analysis of the HLA class II interaction with Epstein-Barr virus glycoprotein 42.

Entry of Epstein-Barr virus (EBV) into B lymphocytes requires the binding of viral glycoprotein 42 (gp42), a C-type lectin family member, to HLA class II. Recently, the structure of the gp42:HLA-DR1 complex was determined. In order to confirm the interaction as determined in the structural study and to identify other potential interactive residues, a mutational analysis of HLA class II was performed. A secreted form of gp42 (sgp42) reacted with a conformation-specific monoclonal antibody and blocked EBV infection. The binding of sgp42 and EBV entry to two sets of HLA class II mutants were tested. The first set of mutants were based on the known interaction of the C-type lectin Ly49A with HLA class I, and the second set of mutants were based on the identified interface in the gp42:HLA-DR1 complex. As expected, none of the mutants that would be predicted to interfere with the interaction of Ly49A with class I affected the interaction of gp42 with HLA class II, whereas mutants in amino acids identified in the gp42:HLA-DR1 structure inhibited sg42 binding to class II. In general, sgp42 binding correlated with efficient entry of EBV, as demonstrated by the necessity of glutamic acid 46 or arginine 72 in class II molecules. Furthermore, other HLA class II residues buried within the interface of gp42 and HLA class II when mutated had either no effect or a decrease in both binding and entry and implicate a region of class II important in stabilizing the interaction with gp42. These studies provide insight into the entry and fusion processes of the critical interaction between gp42 and HLA class II.

Amino Acid Sequence↗

PubMed2004

Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication.

Integrase has been implicated in human immunodeficiency virus type 1 (HIV-1) nuclear import. Integrase analyses, however, can be complicated by the pleiotropic nature of mutations: whereas class I mutants are integration defective, class II mutants display additional assembly and/or reverse transcription defects. We previously determined that HIV-1(V165A), originally reported as defective for nuclear import, was a class II mutant. Here we analyzed mutants containing changes in other putative nuclear localization signals, including (186)KRK(188)/(211)KELQKQITK(219) and Cys-130. Previous work established HIV-1(K186Q), HIV-1(Q214L/Q216L), and HIV-1(C130G) as replication defective, but phenotypic classification was unclear and nuclear import in nondividing cells was not addressed. Consistent with previous reports, most of the bipartite mutants studied here were replication defective. These mutants as well as HIV-1(V165A) synthesized reduced cDNA levels, but a normal fraction of mutant cDNA localized to dividing and nondividing cell nuclei. Somewhat surprisingly, recombinant class II mutant proteins were catalytically active, and class II Vpr-integrase fusion proteins efficiently complemented class I mutant virus. Since a class I Vpr-integrase mutant efficiently complemented class II mutant viruses under conditions in which class II Vpr-integrases failed to function, we conclude that classes I and II define two distinct complementation groups and suggest that class II mutants are primarily defective at a postnuclear entry step of HIV-1 replication. HIV-1(C130G) was also defective for reverse transcription, but Vpr-integrase(C130G) did not efficiently complement class I mutant HIV-1. Since HIV-1(C130A) grew like the wild type, we conclude that Cys-130 is not essential for replication and speculate that perturbation of integrase structure contributed to the pleiotropic HIV-1(C130G) phenotype.

Active Transport, Cell Nucleus↗

PubMed1992

Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.

BACKGROUND: Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times. METHODS AND RESULTS: Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy. CONCLUSIONS: An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug-induced torsade de pointes.

Aged↗

PubMed2001

Characteristic features and ligand specificity of the two olfactory receptor classes from Xenopus laevis.

Amphibia have two classes of olfactory receptors (ORs), class I (fish-like receptors) and class II (mammalian-like receptors). These two receptor classes correspond to the two classes identified in other vertebrates, and amphibians thus provide a unique opportunity to compare olfactory receptors of both classes in one animal species, without the constraints of evolutionary distance between different vertebrate orders, such as fish and mammals. We therefore identified the complete open reading frames of class I and class II ORs in Xenopus laevis. In addition to allowing a representative comparison of the deduced amino acid sequences between both receptor classes, we were also able to perform differential functional analysis. These studies revealed distinct class-specific motifs, particularly in the extracellular loops 2 and 3, which might be of importance for the interaction with odorants, as well as in the intracellular loops 2 and 3, which might be responsible for interactions with specific G-proteins. The results of functional expression studies in Xenopus oocytes, comparing distinct receptor types, support the idea that class I receptors are activated by water-soluble odorants, whereas class II receptors are activated by volatile compounds.

Amino Acid Sequence↗

PubMed1988

Clinical and electrocardiographic characteristics of responders and nonresponders to class IA antiarrhythmic drugs.

A retrospective analysis of 44 patients was carried out to evaluate the efficacy of class IA antiarrhythmic drugs (disopyramide and/or procainamide), and of drugs of one or more other classes by means of 24-hour Holter recording. This study included only patients who exhibited 5000 or more ventricular premature complexes (VPCs) during a 24-hour pretrial baseline recording. The drugs that reduced the frequency of VPCs by at least 50% were considered effective. Eighteen patients (41%) responded to class IA drugs (responders) and 26 patients (59%) did not (nonresponders). There was a significant difference between the two groups in relation to the types of disease (p less than 0.01), but no significant difference with regard to other clinical and electrocardiographic characteristics. There was a significant discordance between trials of class IA drugs and class IC drugs (p less than 0.05). The efficacy of class IA drugs is very similar to that of class IB drugs, and only class IC drugs represent the highest efficacy in patients refractory to both class IA and class IB drugs. In conclusion, when ventricular arrhythmias do not respond to class IA or IB drugs, class IC drugs could be chosen as the next regimen.

Adult↗

PubMed2003

Class size, pupil attentiveness and peer relations.

BACKGROUND: Despite a long-running debate over the effects of class size differences on educational performance there is little evidence on the classroom processes that might be involved. AIMS: The effects of class size differences are examined in relation to social and behavioural adjustment to school, in terms of two dimensions: attentiveness and peer relations. It was predicted that as class size increased there would be more inattentiveness in class and more signs of social difficulties between children in the form of more rejection, asocial, anxious and aggressive behaviour, and less prosocial behaviour. SAMPLES: Data came from a large-scale longitudinal study of children over KS1 (4-7 years). The observation study was based on a subsample of 235 children in 21 small (average 19 children) and 18 large (average 33 children) reception classes (aged 5 years). The PBR sample involved over 5,000. METHODS: There were two complementary methods of data collection: first, a systematic observation study of pre-selected target children in terms of three 'social modes' - when with their teachers, other children and when not interacting - and in terms of work, procedural, social and off-task activities; and, second, a teacher administered Pupil Behaviour Rating (PBR) scale comprising over 50 items rated on a 3-point scale grouped into six 'factors': hyperactive/distractible, aggressive, anxious/ fearful, prosocial, asocial, and excluded. RESULTS: Observations showed that children in large classes were more likely to show off-task behaviour of all kinds, and more likely to interact with their peers in terms of off-task behaviour, social, and also on-task behaviours. Connections between class size and PBR factors were not strong. There was no support for the view that peer relations are better in smaller classes; indeed, there was a slight tendency for worse peer relations, in terms of aggression, asocial and excluded, in the smallest classes. CONCLUSIONS: There was confirmation that children in large classes are more distracted from work and more often off task. The unexpected result, based on teacher ratings, that small classes may lead to less social and more aggressive relations between children is discussed, along with implications for teachers of a tendency for more peer-related contacts in large classes.

Attention↗

PubMed2000

Conservation of Mhc class III region synteny between zebrafish and human as determined by radiation hybrid mapping.

In the HLA, H2, and other mammalian MHC:, the class I and II loci are separated by the so-called class III region comprised of approximately 60 genes that are functionally and evolutionarily unrelated to the class I/II genes. To explore the origin of this island of unrelated loci in the middle of the MHC: 19 homologues of HLA class III genes, we identified 19 homologues of HLA class III genes as well as 21 additional non-class I/II HLA homologues in the zebrafish and mapped them by testing a panel of 94 zebrafish-hamster radiation hybrid cell lines. Six of the HLA class III and eight of the flanking homologues were found to be linked to the zebrafish class I (but not class II) loci in linkage group 19. The remaining homologous loci were found to be scattered over 14 zebrafish linkage groups. The linkage group 19 contains at least 25 genes (not counting the class I loci) that are also syntenic on human chromosome 6. This gene assembly presumably represents the pre-MHC: that existed before the class I/II genes arose. The pre-MHC: may not have contained the complement and other class III genes involved in immune response.

Animals↗

PubMed1992

Broad recognition of cytotoxic T cell epitopes from the HIV-1 envelope protein with multiple class I histocompatibility molecules.

A few cases have been described of antigenic determinants that are broadly presented by multiple class II MHC molecules, especially murine I-E or human DR, in which polymorphism is limited to the beta chain, and the alpha chain is conserved. However, no similar cases have been studied for presentation by class I MHC molecules. Because both domains of the MHC peptide binding site are polymorphic in class I molecules, exploring permissiveness in class I presentation would be of interest, and also such broadly presented antigenic determinants would clearly be useful for vaccine development. We had defined an immunodominant determinant, P18, of the HIV-1 gp160 envelope protein recognized by human and murine CTL. To determine the range of class I MHC molecules that could present this peptide and to determine whether two HIV-1 gp160 Th cell determinants, T1 and HP53, could also be presented by class I MHC molecules, we attempted to generate CTL specific for these three peptides in 10 strains of B10 congenic mice, representing 10 MHC types, and BALB/c mice. P18 was presented by at least four different class I MHC molecules from independent haplotypes (H-2d, p, u, and q to CD8+ CTL. In H-2d and H-2q the presentation was mapped to the D-end class I molecule, and for Dd, a requirement for both the alpha 1 and alpha 2 domains of Dd, not Ld, was found. HP53 was also presented by the same four different class I MHC molecules to CD8+ CTL although at higher concentrations. T1 was presented by class I molecules in three different strains of distinct MHC types (B10.M, H-2f; B10.A, H-2a; and B10, H-2b) to CTL. The CTL specific for P18 and HP53 were shown to be CD8+ and CD4- and to kill targets expressing endogenously synthesized whole gp160 as well as targets pulsed with the corresponding peptide. To compare the site within each peptide presented by the different class I molecules, we used overlapping and substituted peptides and found that the critical regions of each peptide are the similar for all four MHC molecules. Thus, antigenic sites are broadly or permissively presented by class I MHC molecules even without a nonpolymorphic domain as found in DR and I-E, and these sequences may be of broad usefulness in a synthetic vaccine.

Amino Acid Sequence↗

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