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A K Jonsson

Publications and source records attributed to A K Jonsson.

14 recordsLinked to original sources
PubMed1991

Characterization of cDNA for human tripeptidyl peptidase II: the N-terminal part of the enzyme is similar to subtilisin.

Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening a human B-lymphocyte cDNA library with a degenerated oligonucleotide mixture. The B-lymphocyte cDNA library and a cDNA library, obtained from human fibroblasts, were rescreened with a 147 bp fragment from the 5' part of the A2 clone, whereby three different overlapping cDNA clones could be isolated. The deduced amino acid sequence, 1196 amino acid residues, corresponding to the longest open reading frame of the assembled nucleotide sequence, was compared to sequences of current databases. This revealed a 56% similarity between the bacterial enzyme subtilisin and the N-terminal part of tripeptidyl peptidase II. The enzyme was found to be represented by two different mRNAs of 4.2 and 5.0 kilobases, respectively, which probably result from the utilization of two different polyadenylation sites. Furthermore, cDNA corresponding to both the N-terminal and C-terminal part of tripeptidyl peptidase II hybridized with genomic DNA from mouse, horse, calf, and hen, even under fairly high stringency conditions, indicating that tripeptidyl peptidase II is highly conserved.

Amino Acid Sequence↗
PubMed1991

Concerted evolution in a segment of the first domain exon of polymorphic MHC class II beta loci.

Genetic exchange of sequence information between members of a gene family, generally denoted gene conversion, causes a phenomenon called "concerted evolution" meaning that non-allelic genes do not evolve independently. The possible significance of this phenomenon in the evolution of major histocompatibility complex (MHC) class II genes has been investigated in the present study. The results of a phylogenetic analysis of human, mouse, bovine, and chicken class II sequences were consistent with the occurrence of gene conversion between polymorphic class II beta genes (i.e. DPB, DQB, and DRB) but not between these genes and the monomorphic DOB gene or between class II alpha genes. Gene conversion between polymorphic beta genes appears to be restricted to a gene segment between approximately nucleotide positions 94-286 in the first domain exon. Due to this genetic exchange, there is a greater interlocus similarity both at the DNA and protein level in this region than in the rest of the sequence. The region encodes a functionally important part of the class II molecule including more than half of the beta-chain residues of the antigen binding site and the residues in the alpha helix assumed to form contact with the T-cell receptor. The observed similarity in the alpha-helical region of class II beta molecules may be functionally significant for the utilization of the T-cell repertoire for antigen recognition in the immune system.

Animals↗
PubMed1991

The structure of human MHC class II genes.

The class II molecules of the human major histocompatibility complex bind intracellularly processed peptides and present them to T-helper cells. They therefore have a critical role in the initiation of the immune response. A salient feature of the class II molecules is their polymorphism. It has been shown that some autoimmune diseases are associated with certain class II alleles. This article reviews the basic structural features of class II molecules, and the genes encoding them as well as mechanisms governing the development of their extraordinary polymorphism.

Autoimmune Diseases↗
PubMed1989

A cellular and functional split in the DRw8 haplotype is due to a single amino acid replacement (DR beta ser 57- asp 57).

The single DR beta chain gene of the DRw8 haplotype has been suggested to carry both the DRw8 and the DRw52 epitopes. Cellular typing has shown that the DRw8 haplotype can be split into three subtypes, Dw8.1, Dw8.2, and Dw8.3, presumably due to a polymorphism in the DRw8 beta chain. Furthermore, Dw8.1 and Dw8.2 cells present influenza virus antigen to different T-cell clones. In the present study, DRw8/Dw8.2 beta chain cDNA was cloned and characterized. A comparison of this sequence with a partial DRw8/Dw8.1 beta chain gene suggested that the DRw8 split is due to a single amino acid replacement of ser57-asp57 caused by three nucleotide substitutions in the same codon. In most DR haplotypes, two expressed DR beta chain genes exist. Comparing the nucleotide sequence of the single beta gene in the DRw8 haplotype to those of other DR beta genes revealed that the DRw8 beta gene sequence is most closely related to the DRB1 genes of the DR3, 5, and w6 haplotypes. However, the comparisons also showed that it was not possible from sequence similarities to divide the DR beta genes into two or more distinct allelic series.

Amino Acid Sequence↗
PubMed1989

Selection for polymorphism in the antigen recognition site of major histocompatibility complex class II molecules.

The genetic basis for the extensive polymorphism of major histocompatibility complex (MHC) class II molecules was investigated by statistical analysis. Nucleotide sequences of human DQA1, DQB1, DRB1, and DRB3 genes and murine A alpha, A beta, and E beta genes were used. The results show that polymorphism is selected for in the antigen recognition site of class II molecules since replacement substitutions in this region were found to occur at a significantly higher frequency than expected in the absence of selection. In contrast, replacement substitutions are selected against in the remaining part of the first domain exon and in the second domain exon. Furthermore, comparing the sequence variability pattern among different class II alpha and beta sequences, using a variability index for each residue, showed that, with few exceptions, highly polymorphic residues occur in the antigen recognition site. There was a strong and highly significant correlation in the variability pattern in the homologous DRB/E beta sequences but not for DQB/A beta or DQA/A alpha sequences. This difference may be related to the fact that both alpha and beta chains of DQ/A molecules are polymorphic, while only beta chains of DR/E molecules vary.

Amino Acid Sequence↗
PubMed1987

Class II genes of the human major histocompatibility complex. Comparisons of the DQ and DX alpha and beta genes.

The human major histocompatibility complex, HLA, contains the genes of several class II molecules. We present here the molecular maps of the DQ and DX subregions and analyze the sequences of the polymorphic DQ alpha and DQ beta genes as well as the DX alpha and DX beta genes. The DQ alpha and DQ beta genes are oriented in opposite directions, approximately 12 kilobases apart. The DX alpha and DX beta genes are similarly oriented about 8 kilobases. The exon-intron organizations of the DQ alpha and DX alpha genes are analogous to those of other class II alpha genes. Comparison of the DQ alpha gene sequence to three DQ alpha cDNA clones shows that amino acid replacements are predominantly located between residues 45 and 80 in the amino-terminal domain. Analysis of the frequency of silent and replacement substitutions indicates that there is little selection against replacements in DQ alpha first domains. The exons encoding the second domains of DQ alpha and DX alpha are virtually identical, suggesting that a gene conversion event has occurred between these genes. The DX beta gene is very similar to the DQ beta gene but differs in the cytoplasmic portion. The DX beta gene contains a separate exon of 24 nucleotides encoding the core of the cytoplasmic tail. This exon is not expressed in the DQ beta genes due to a nonfunctional splice junction. Comparison of the number of nucleotide substitutions in the DQ beta first and second domain exons suggests that little or no phenotypic selection acts on the first domain whereas the second domain is under strong selection.

Amino Acid Sequence↗
PubMed1987

Class II genes of the human major histocompatibility complex. Evolution of the DP region as deduced from nucleotide sequences of the four genes.

The DP region of the human major histocompatibility complex contains two alpha genes and two beta genes. The DP alpha 1 and beta 1 genes encode the expressed DP histocompatibility antigen molecule, while the DP alpha 2 and beta 2 genes are inactive in the haplotypes examined. Here we present the sequence of the two DP beta genes and of the expressed DP alpha 1 gene. Nucleotide sequence comparisons reveal a considerably greater degree of similarity between the two beta genes than between the two alpha genes. We propose that a duplication giving rise to the DP alpha gene pair evolutionarily preceded the corresponding DP beta gene duplication. We also propose, based on the orientation of other class II gene pairs, that the original DP molecule was encoded by the DP beta 1 and DP alpha 2 genes. At some stage during the evolution of the DP region both of the two pseudogenes appear to have been expressed.

Amino Acid Sequence↗
PubMed1984

Both alpha and beta chains of HLA-DC class II histocompatibility antigens display extensive polymorphism in their amino-terminal domains.

At least three class II antigens, all composed of an alpha and a beta subunit, are encoded in the human major histocompatibility complex, i.e., DR, DC and SB. Two cDNA clones, encoding a DC alpha and a DC beta chain, respectively, were isolated from a cDNA library of the lymphoblastoid cell line Raji (DR3,w6). The two polypeptides predicted from the nucleotide sequences of these clones are each composed of a signal peptide, two extracellular domains, a hydrophobic transmembrane region and a short cytoplasmic tail. Comparison of the DC alpha sequence with two previously published partial sequences shows that the majority of the differences is located in the amino-terminal domain. The differences are not randomly distributed; a cluster of replacements is present in the central portion of the amino-terminal domain. Likewise, the allelic polymorphism of the DC beta chains occurs preferentially in the amino-terminal domain, where three minor clusters of replacements can be discerned. The non-random distribution of the variability of DC alpha and beta chains may be due to phenotypic selection against replacement substitutions in the second domains of the polypeptides.

Amino Acid Sequence↗
PubMed1981

A rapid method for purification of human granulocytes using percoll. A comparison with dextran sedimentation.

A simple one-step method for purification of human granulocytes, based on the use of a discontinuous gradient of Percoll, is described. The cell yield is 55% and the purity of the granulocyte fraction is 97%. The cells' ability to exclude trypan blue and phagocytic function are not altered during the purification process. We conclude that centrifugation in Percoll is superior to conventional dextran sedimentation; it is also less time-consuming.

Cell Separation↗