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A Corell

Publications and source records attributed to A Corell.

At least 37 records · Page 2Linked to original sources
PubMed1994

C4 gene polymorphism in primates: evolution, generation, and Chido and Rodgers antigenicity.

Eleven new C4d genomic primate sequences of the fourth complement factor (C4) have been obtained. Seven of them belong to five species not yet explored for this gene: Pan paniscus (pygmy chimpanzee), Cercopithecus aethiops (green monkey), Macaca mulatta (rhesus monkey), Macaca fascicularis (cynomolgus), and Saguinus oedipus (cotton top tamarin). The New World monkeys (tamarins, four individuals) sequenced for C4 have a single C4d sequence only, which shows a B isotypic specificity and a Rodgers 3 (Rg3), Chido 1 (Ch1) antigenicity. Rg3 and Ch1 could thus be the oldest Rg/Ch specificity (at least 50 million years old) and Rg1, Rg2, Ch3, and Ch6 could be more recent human-specific antigens. Mechanisms of C4d polymorphism generation were analyzed by compiling all the presently available sequences. Examples of both point mutations and crossing-over events among C4d primate sequences could be detected. The problem of a possible trans-species inheritance of C4d polymorphism was addressed and two apparently contradicting dendrograms were obtained. One of them, constructed by using both exon and intron sequences, does not support trans-species evolution, but supports the proposed theory of extensive homogenization of the C4 genes occurring within each species, because alleles from each primate species cluster together. Another completely different dendrogram, obtained by using exon sequences only, suggests the existence of trans-species evolution for C4d polymorphism, because alleles belonging to different species cluster together in a way similar to that found for HLA class I or II alleles. However, orangutan sequences group together in both kinds of C4d sequence dendrograms and seem to have arisen from an ancestor different from that of chimpanzee, gorilla and man C4d sequences. Finally, further data have been obtained that support trans-species conservation of A-ness and B-ness and the existence of trans-specifically conserved allelic motifs, both in intronic and exonic sequences.

Amino Acid Sequence↗
PubMed1994

Peripheral blood reduction of memory (CD29+, CD45RO+, and "bright" CD2+ and LFA-1+) T lymphocytes in Papillon-Lefèvre syndrome.

A Papillon-Lefèvre patient with characteristic chronic periodontal disease and palmoplantar keratoderma was studied over a 4-year period. An abnormal T-cell phenotype was steadily observed in peripheral blood; both low numbers of CD29+ and CD45RO+ cells and a low density surface expression of CD2 and LFA-1 molecules were found. T-cell activation through CD3, CD2 and ConA, PWM and IL-2 receptors was normal; however, there was impairment in the activation via CD28. CD2, LFA-1 and CD45 molecules were normal in charge and molecular weight. There was no tissue sequestering of T lymphocytes in periodontal lesions, but rather a relative T-cell reduction. It is suggested that an important decrease of the so-called "memory/hyperreactive" (CD45RO-positive) T cells does exist; therefore, hyperreactive T cells would not be available in sufficient numbers to leave the bloodstream through blood vessel endothelium, and the periodontium would be left without these important defenses and thus exposed to chronic infections. A disregulated factor affecting the transition from "naive" to "memory" T cells and the increase in certain surface molecules expression (i.e., CD2, LFA-1, CD29, and CD45RO) or the reversion from memory to naive T cells may be responsible for the disease pathogenesis. CD2 and LFA-1 molecule synthesis might be conjointly regulated on T lymphocytes.

Adolescent↗
PubMed1994

New species-specific alleles at the primate MHC-G locus.

Six different ape MHC-G DNA sequences (four in humans: HLA-G*01011, HLA-G*II, HLA-G*0103, and HLA-G*IV; one in chimpanzees: Patr-G*I; and one in gorillas: Gogo-G*1) have been obtained. Only synonymous or conservative ("Thr"-to-"Ser") substitutions are allowed between the four human alleles. One allele of MHC-G exon-2 sequences has been found both in gorilla (Gorilla gorilla) and chimpanzee (Pan troglodytes). The Patr-G*I DNA sequence shows two nonsynonymous substitutions when compared with the human HLA-G*01011 sequence: "CGG"-to-"TGG" ("Arg"-to-"Trp") at codon 35 and "ATG"-to-"ATA" ("Met"-to-"Ile") at codon 76. One nonsynonymous "GAG"-to-"GGG" ("Glu"-to-"Gly") substitution is observed in the Gogo-G*I exon-2 DNA sequence, when compared with the human *01011 allele. None of these three different substitutions have been observed in humans and are, thus, considered species specific. Also, evidence is provided that the human HLA-G*II and G*0103 may have been originated after human speciation. Finally, phylogenetic relationships among the six MHC-G alleles, tamarins G-"like" alleles, and other human class I genes (both "classical" and "nonclassic") are discussed.

Alleles↗
PubMed1994

Primary T lymphocyte immunodeficiency associated with a selective impairment of CD2, CD3, CD43 (but not CD28)-mediated signal transduction.

A 2-year-old female with important signs of immune response failure against virus, bacteria, fungi and protozoa and no obvious humoral or lymphocyte phenotypical defect was studied. Both peripheral blood mononuclear cells and IL-2-dependent T cell lines derived from the patient showed a severe selective T cell activation impairment via CD2, CD3 and CD43; however, this defect was reversible with the addition of either IL-2, or phorbol myristate acetate (PMA) or anti-CD28 antibodies. Concordantly, the induction of IL-2 (and, in part, IL-3 and IL-4) messenger RNA was severely reduced in stimulated T cells, but that of other cytokines was either normal (IL-5) or only slightly diminished (interferon-gamma (IFN-gamma)). It is concluded that an activation T cell defect exists previous to protein kinase C (PKC) and between membrane receptors and the activation pathway of certain response genes encoding for interleukins involved in proliferation (i.e. IL-2, IL-3 and IL-4), but not of others (i.e. IL-5). The use of T cell lines from human T lymphocyte activation deficiencies allows dissection of T cell pathology and the corresponding physiological pathways. In the present description, there is an evident independence of the CD28 T cell activation pathway from those induced through CD2 or CD3, and the differential gene regulation of the different interleukins.

Antigens, CD↗
PubMed1993

Differential contribution of C4 and HLA-DQ genes to systemic lupus erythematosus susceptibility.

The particular histocompatability antigen (HLA) gene(s) that may confer systemic lupus erythematosus (SLE) susceptibility remains unknown. In the present study, 58 unrelated patients and 69 controls have been analyzed for their class I and class II serologic antigens, class II (DR and DQ) DNA restriction fragment length polymorphism, their deduced DQA1 and B1 exon 2 nucleotide sequences and their corresponding amino acid residues. By using the etiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative SLE susceptibility locus, it has been found that the strength of association of the HLA marker may be quantified as follows: DQA1*0501 (associated to DR3) or DQB1*0201 (associated to DR3) > non Asp 57 beta DQ/Arg 52 alpha DQ > DR3 > non Asp 57 beta DQ. Thus, molecular HLA DQ markers tend to be more accurate as susceptibility markers than the classical serologic markers (DR3). However, dominant or recessive non Asp 57 beta DQ susceptibility theories, as previously postulated for insulin-dependent diabetes mellitus, do not hold in our SLE nephritic population; indeed, three patients bear neither Arg 52 alpha DQ nor Asp 57 beta DQ suscepibility factors. On the other hand, nonsusceptibility factors are included in our population in the A30B18CF130-DR3DQ2(Dw25) haplotype and not in A1B8CS01-DR3DQ2(Dw24); this distinctive association has also been recorded in type I diabetes mellitus and may reflect the existence of common pathogenic HLA-linked factors for both diseases only in the A30B18CF10DR3DQ2(Dw25) haplotype. Finally, the observed increase of deleted C4 genes (and not 'null' C4 proteins) in nephritic patients shows that C4 genes are disease markers, but probably without a pathogenic role.

Complement C4↗
PubMed1993

Three new HLA-G alleles and their linkage disequilibria with HLA-A.

Three new allelic forms of the HLA-G DNA sequence (HLA-G*II, HLA-G*III, and HLA-G*IV) have been identified. With the HLA-G*I sequence (previously designated HLA 6.0) as a reference, HLA-G*II shows a silent (G-->A) mutation at the third base of codon 57, HLA-G*III bears a non-synonymous (A-->T), but conservative, (Thr-->Ser) substitution at the first base of codon 31, and HLA-G*IV shows two silent substitutions: (A-->T) at the third base of codon 107 and (G-->A) at the third base of codon 57. A rapid method of singling out each allele on genomic DNA has been developed by using polymerase chain reaction amplification followed by restriction endonuclease treatment. Also, more or less strong linkage disequilibria has been found between most HLA-A alleles and either HLA-G*I or *II, both being the most prevalent alleles in the population, with a genotypic frequency of 0.55 and 0.38, respectively; HLA-G*III is very rare and HLA-G*IV has a genotypic frequency of 0.07. An evolutive classification of HLA-A alleles results according to their association with either HLA-G*I or HLA-G*II, which does not correlate with the classical serological cross-reacting groups classification. The finding of a strong and selective A/G linkage disequilibria with most HLA-A alleles, together with the existence of less frequent random A/G associations, may suggest that there exist in different haplotypes true and varied A/G genetic distances (and not a recombinational hotspot). It may be inferred from preliminary data that in primates HLA-A/G haplotypes bearing G*II may have appeared later than those bearing G*I.

Alleles↗
PubMed1992

Allelic diversity at the primate major histocompatibility complex DRB6 locus.

The HLA-DRB6 gene (also called DRB sigma/V1) has been found only in about 26% of human HLA haplotypes, i.e.; DR1, DRw10, and DR2-bearing ones (Corell et al. 1991). In contrast, exon-2 DRB6 sequences have been obtained from all tested primates: nine chimpanzees (Pan troglodytes), three gorillas (Gorilla gorilla) and three orangutans (Pongo pygmaeus); other apes which had already been sequenced (one gorilla and one chimpanzee) also had the DRB6 gene. Thus, all apes tested from three different species, some of them evolutionary separated by at least 14-16 million years, bear the DRB6 gene. In addition, more than one gene copy per haplotype has been found in one chimpanzee; this, together with the apparent loss of this gene in some of the human DR haplotypes, may indicate that the DR genome has undergone evolutionary changes more recently and more actively than class I or III genes. In addition, ten different and presumably allelic DRB6 exon-2 sequences have been obtained, and some of them coming from different species are more similar to each other than the one from the same species; this finding goes in favor of the trans-species theory of major histocompatibility complex polymorphism generation. Also, data are presented supporting that DRB6 may be one of the eldest genes of the DRB family, thus one of the first to diverge from the ancestral DRB gene.

Alleles↗
PubMed1992

Comparison between HLA-DRB and DQ DNA sequences and classic serological markers as type 1 (insulin-dependent) diabetes mellitus predictive risk markers in the Spanish population.

The question of HLA susceptibility to Type 1 (insulin-dependent) diabetes mellitus remains unresolved. In the present study, 127 diabetic patients and 177 unrelated control subjects have been analysed for their class I and class II serological antigens, class II (DR, DQ) DNA restriction fragment length polymorphisms and DQA1 and B1 exon-2 nucleotide sequences and their corresponding amino acid residues. By using the aetiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative Type 1 diabetes susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DR4 less than DR3 less than DR3 or DR4 less than non-Aspartate 57 beta DQ and Arginine 52 alpha DQ less than Arginine 52 alpha DQ. Thus, molecular HLA-DQ markers appear to be more accurate as susceptibility markers than the classic serologically defined ones (DR3 and DR4); however, any effect of DQ markers disappears when non-DR3/DR4 individuals are considered, suggesting that DR factors (or others in between DQ and DR) are also important. In addition, a dominant non-Aspartate 57 beta DQ susceptibility theory does not hold (but a recessive one does) in our diabetic population (probably due to the high frequency of the protective DR7-non-Aspartate 57 beta DQ haplotypes); Arginine 52 alpha DQ is the best single HLA marker found in our population, both as a recessive or as a dominant one. Also there are 13 patients in our sample who bear neither Arginine 52 alpha DQ nor non-Aspartate 57 beta DQ susceptibility factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Vaginal infection of mice with HSV type 2 variant ER-: a new animal model for human primary genital HSV type 2 infections.

Studying the pathogenesis of vaginal infections in mice with two variants of Herpes simplex virus type 2 (HSV-2) strain ER we observed that both variants ER+ and ER- caused severe vaginitis but only ER+ invaded the CNS leading to lethal neurological disease. In contrast, mice infected with ER- cleared the virus from the vagina and recovered from infection. ER+ and ER- expressed equal levels of thymidine kinase (TK) indicating a TK-independent difference in neurovirulence. Using the non-neurovirulent variant ER-, we were able to investigate humoral immune responses later after infection. Vaginal infection with ER- suppressed serum antibody formation after a secondary systemic HSV-1 infection. Fresh isolates of HSV-1 and HSV-2 caused uniformly a lethal neurological disease after vaginal inoculation of mice. However, some animals survived an intraperitoneal infection with these isolates. Infection with HSV-1 isolates stimulated a strong antibody production, whereas infection with HSV-2 isolates suppressed antibody formation, thus supporting earlier results from our group obtained with laboratory strains. Since suppression of antibody formation could be demonstrated with clinical HSV-2 isolates and likewise after vaginal infection with HSV-2 variant ER- we consider this phenomenon to be of relevance in human genital HSV-2 infections. Vaginal infection of mice with variant ER- represents a new model for primary genital HSV-2 infections; this model could be useful for histopathological, virological, immunological and drug testing studies.

Animals↗
PubMed1992

Human T-cell activation deficiencies.

The increasing understanding of T-cell activation is paralleled by the recognition of a growing range of 'experiments of nature' that cause T-cell activation deficiencies. Analysis of these deficiencies is, in turn, contributing to the understanding of T-cell function in vivo. Here, José Regueiro, Antonio Arnaiz-Villena and colleagues review current knowledge of structural and functional T-cell defects and the implications of these for T-cell biology.

Adenosine Deaminase↗
PubMed1992

From pathology to physiology of the human T-lymphocyte receptor.

The recent description of a selective human CD3 gamma deficiency and other T-cell receptor (TCR)/CD3 structural and functional defects, together with previous biochemical data on the structure and interactions of the TCR/CD3 complex, may aid in elucidating the physiology of this multi-subunit membrane ensemble. CD3 gamma seemed to be required for the commitment and thymic maturation of an important fraction of T lymphocytes to the CD8 (but not CD4) lineage, perhaps by participating with the CD8 co-receptor in the instructive signal delivered through the alpha beta TCR during intrathymic positive selection by HLA class I molecules. The homologous CD3 delta component would, in contrast, be necessary for the selection of CD4 lymphocytes by HLA class II molecules. The interaction of CD4 and CD8 with the TCR/CD3 complex during antigen recognition may thus be asymmetrical, taking place through CD3 delta and gamma, respectively. Also, the existence of in vivo functional TCR/CD3 hemireceptors (lacking either CD3 gamma or CD3 delta) is suggested, and defects in their relative amount on the T-cell surface may disrupt unresponsiveness to self antigens and generate autoimmunity.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

The HLA-DRB6 locus defines an evolutionary supratypic group within the DRB family of genes.

A novel DRB gene member has recently been identified (DRB6). It defines a new supratypic group of HLA-DR alleles comprising the DR1-, DR2-, and DRw10-carrying haplotypes. The comparison of this gene either at the nucleotide or at the protein level with other HLA-DRB genes supports its inclusion in the DRB gene family and not in DPB or DQB gene families. Moreover, the construction of an evolutionary gene-tree shows that this gene is probably the eldest member of the DRB gene family. Contradictory expression results do not clarify whether or not DRB6 is a pseudogene.

Base Sequence↗