P1609HLA EPITOPE MATCHING IN KIDNEY TRANSPLANTATION AND PRACTICAL APPLICATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irena Rambabova Bushljetikj ◽  
Goce Spasovski ◽  
Koco Dimitrovski
Keyword(s):  
Kidney Transplantation ◽  
Amino Acid ◽  
Acute Rejection ◽  
Amino Acid Sequences ◽  
Class I ◽  
Hla Dr ◽  
Increased Risk ◽  
Class 1 ◽  
Unrelated Donors ◽  
Hla Mismatches

Abstract Background and Aims HLA compatibility between donor and recipient is an important factor that influences graft outcomes after kidney transplantation. Increasing number of class I (HLA-AB) and class II (HLA-DR) mismatches are associated with an increased risk of acute rejection and graft loss. Recent developments have increased our understanding of the structural basis of HLA antigenicity and may allow accurate evaluation of the immunogenic potential of broad antigen HLA mismatches. The immunogenicity of HLA antigens is determined by continuous and discontinuous short sequences of amino acids that form the antibody-accessible regions within each HLA allele known as epitopes. HLAMatchmaker, a computer algorithm that calculates the number of epitope mismatches between donors and recipients by considering each HLA allele as a combination of distinct epitopes known as triplets (continuous amino acid sequences) or eplets (closely located contiguous amino acid sequences). Method A total number of 55 adult patients with LDKT were included in the study. The inclusion criteria: first transplantation of one organ - kidney, use of living donor related or unrelated, emotionally related (spouses) donor. Data concerning donor - sex, age of the donor, type of donation (related or unrelated donor), and data concerning the recipients: sex, age, hemodialysis vintage, underlying disease, type of immunosuppressive therapy, were analyzed. The number of eplet HLA mismatches for each recipient and donor pair at HLA class I (HLA-AB) and class II (HLA-DR) loci was calculated using HLAMatchmaker (Version 1.2) Results In our study we have included 55 patients. 44 patients have related and 11 have unrelated donors. From the group of related donors 31 patients were haploidentycal, with 3 HLA miss match, in the group of unrelated donors-recipients 5 of them have 6 miss match. According HLA MM triplets Class 1 + 2 < or> 20 we have devided 2 groups, but no statistical difference on the graft function was observed in the follow up period. Three acute rejections were reported in the group of patients with HLA miss match triplets Class 1 + 2> 20. Conclusion An increasing number of epitope HLA mismatches is associated with an increased risk of acute rejection. Triplet HLA mismatches may provide better risk stratification for acute rejection and graft survival among those who are otherwise classified as low immunological risk at the broad antigen level.

PR3-ANCA-associated vasculitis is associated with a specific motif in the peptide-binding cleft of HLA-DP molecules

Rheumatology ◽  
2019 ◽  
Vol 58 (11) ◽  
pp. 1942-1949 ◽  
Author(s):  
Jon Waarst Gregersen ◽  
Christian Erikstrup ◽  
Per Ivarsen ◽  
Rie Glerup ◽  
Elizabeth Krarup ◽  
...  
Keyword(s):  
Amino Acid ◽  
Peptide Binding ◽  
Amino Acid Sequences ◽  
Homogeneous Population ◽  
Exon 2 ◽  
Hla Alleles ◽  
Hypervariable Regions ◽  
Anca Associated Vasculitis ◽  
Increased Risk ◽  
Kidney Involvement

Abstract Objectives This study aimed to characterize the association between HLA alleles and ANCA-associated vasculitis (AAV) in a genetically homogeneous population, and to analyse the contribution of specific HLA molecule amino acid sequences to the risk of AAV. Methods We included 187 Danish patients with AAV and 1070 healthy controls. All were HLA typed at two-field resolution. The association of HLA alleles to PR3- or MPO-AAV was analysed. The contribution of the dominant molecular motifs of the HLA-DPB1 molecule to the risk of AAV was investigated by association studies that included specific amino acid sequences of the hypervariable regions in exon 2. Results Ninety-four percent of patients with PR3-AAV were carriers of HLA-DPB1*04:01 while all patients with PR3-AAV were carriers of an HLA-DPB1*04 allele, and 85% were homozygous. This was significantly more than in the control group (P < 0.0001). The association was even stronger when HLA-DPB1*04:02 and -DPB1*23:01 were included. HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01 share amino acids in positions 8–9, 69, 76 and 84–87 within the hypervariable regions, but only positions 69 and 84–87 contributed significantly to the disease risk. HLA-DRB1*15 was associated with an increased risk of developing PR3-AAV, while HLA-DRB1*04, -DRB1*07 and -DQB1*03 were associated with a reduced risk of kidney involvement in PR3-AAV. MPO-AAV was only weakly associated with HLA class I alleles. Conclusion PR3-AAV is strongly associated with the HLA-DPB1 alleles HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01, which share amino acid sequences crucial for the peptide-binding groove.

scholarly journals Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis. Synthetic peptides define the epitopes responsible for serosubtype specificity.

1990 ◽  
Vol 171 (6) ◽  
pp. 1871-1882 ◽  
Author(s):  
B McGuinness ◽  
A K Barlow ◽  
I N Clarke ◽  
J E Farley ◽  
A Anilionis ◽  
...  
Keyword(s):  
Amino Acid ◽  
Solid Phase ◽  
Protein Molecule ◽  
Amino Acid Sequences ◽  
Structural Homology ◽  
Gene Encoding ◽  
Subtype Specificity ◽  
Class 1 ◽  
Variable Domains ◽  
Major Variation

The previously determined nucleotide sequence of the porA gene, encoding the class 1 outer membrane protein of meningococcal strain MC50, has been used to clone and sequence the porA gene from two further strains with differing serosubtype specificities. Comparison of the predicted amino acid sequences of the three class 1 proteins revealed considerable structural homology with major variation confined to two discrete regions (VR1 and VR2). The high degree of structural homology between the sequences gave predicted secondary structures that were almost identical, with the variable domains located in hydrophilic regions that are likely to be surface located and hence accessible to antibody binding. The predicted amino acid sequences have been used to define the epitopes recognized by mAbs with serosubtype specificity. A series of overlapping decapeptides spanning each of the class 1 protein sequences have been synthesized on solid-phase supports and probed with mAbs. Antibodies with P1.16 and P1.15 subtype specificity reacted with sequences in the VR2 domain, while antibodies with P1.7 subtype specificity reacted with sequences in the VR1 domain. Further peptides have been constructed to define the minimum epitopes recognized by each antibody. Thus we have been able to define linear peptides on each class 1 protein molecule that are responsible for subtype specificity and that represent targets for a protective immune response.

scholarly journals The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation

2016 ◽  
Vol 2 (12) ◽  
pp. e120 ◽  
Author(s):  
Hung Thanh Do Nguyen ◽  
Germaine Wong ◽  
Jeremy R. Chapman ◽  
Stephen P. McDonald ◽  
Patrick T. Coates ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Hla Mismatches

scholarly journals Relationship of donor-specific class-I anti-HLA antibodies detected by ELISA after kidney transplantation on the development of acute rejection and graft survival

2003 ◽  
Vol 18 (5) ◽  
pp. 990-995 ◽  
Author(s):  
G. Fernandez-Fresnedo ◽  
J. M. Pastor ◽  
M. Lopez-Hoyos ◽  
J. C. Ruiz ◽  
J. A. Zubimendi ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Graft Survival ◽  
Class I ◽  
Specific Class ◽  
Hla Antibodies ◽  
Relationship Of

scholarly journals Outcomes of kidney transplantation over a 16-year period in Korea: An analysis of the National Health Information Database

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247449
Author(s):  
Hyung Soon Lee ◽  
Minjin Kang ◽  
Banseok Kim ◽  
Yongjung Park
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Health Insurance ◽  
Acute Rejection ◽  
Health Information ◽  
National Health ◽  
Graft Failure ◽  
Survival Rates ◽  
Increased Risk ◽  
Information Database

Background This study investigated the outcomes of kidney transplantation (KT) over a 16-year period in Korea and identified risk factors for graft failure using a nationwide population-based cohort. Methods We investigated the Korean National Health Insurance Service-National Health Information Database. Health insurance claims for patients who underwent KT between 2002 and 2017 were analyzed. Results The data from 18,331 patients who underwent their first KT were reviewed. The percentage of antithymocyte globulin (ATG) induction continuously increased from 2.0% in 2002 to 23.5% in 2017. Rituximab began to be used in 2008 and had increased to 141 patients (9.6%) in 2013. Acute rejection occurred in 17.3% of all patients in 2002 but decreased to 6.3% in 2017. The rejection-free survival rates were 78.8% at 6 months after KT, 76.1% after 1 year, 67.5% after 5 years, 61.7% after 10 years, and 56.7% after 15 years. The graft survival rates remained over 80% until 12 years after KT, and then rapidly decreased to 50.5% at 16 years after KT. In Cox’s multivariate analysis, risk factors for graft failure included being male, more recent KT, KT from deceased donor, use of ATG, basiliximab, or rituximab, tacrolimus use as an initial calcineurin inhibitor, acute rejection history, and cytomegalovirus infection. Conclusions ATG and rituximab use has gradually increased in Korea and more recent KT is associated with an increased risk of graft failure. Therefore, meticulous preoperative evaluation and postoperative management are necessary in the case of recent KT with high risk of graft failure.

scholarly journals Partial DnaK protein expression from Coxiella-like endosymbiont of Rhipicephalus annulatus tick

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249354
Author(s):  
Pornpiroon Nooroong ◽  
Wachareeporn Trinachartvanit ◽  
Visut Baimai ◽  
Panat Anuracpreeda ◽  
Arunee Ahantarig
Keyword(s):  
Amino Acid ◽  
Q Fever ◽  
Amino Acid Sequences ◽  
Nucleotide Substitutions ◽  
Mhc I ◽  
Mhc Ii ◽  
Hla Dr ◽  
Rhipicephalus Annulatus ◽  
Obligate Intracellular Bacteria ◽  
Dnak Protein

Q fever is one of the most important zoonotic diseases caused by the obligate intracellular bacteria, Coxiella burnetii. This bacterial infection has been frequently reported in both humans and animals, especially ruminants. Ticks are important ectoparasite and serve as reservoir hosts of Coxiella-like endosymbionts (CLEs). In this study, we have attempted to express chaperone-coding genes from CLEs of Rhipicephalus annulatus ticks collected fromcow path. The partial DnaK coding sequence has been amplified and expressed by Escherichia coli. Amino acid sequences have been analyzed by MS-MS spectrometry and the UniProt database. Despites nucleotide sequences indicating high nucleotide variation and diversity, many nucleotide substitutions are synonymous. In addition, amino acid substitutions compensate for the physicochemical properties of the original amino acids. Immune Epitope Database and Analysis Resource (IEDB-AR) was employed to indicate the antigenicity of the partial DnaK protein and predict the epitopes of B-and T-cells. Interestingly, some predicted HLA-A and B alleles of the MHC-I and HLA-DR alleles belonging to MHC-II were similar to T-cell responses to C. burnetii in Q fever patients. Therefore, the partial DnaK protein of CLE from R. annulatus could be considered a vaccine candidate and immunogenic marker with future prospects.

scholarly journals The subunit structure of rabbit skeletal-muscle phosphofructokinase and the amino acid sequence of the tryptic peptide containing the highly reactive thiol group

1977 ◽  
Vol 163 (2) ◽  
pp. 309-316 ◽  
Author(s):  
I A Simpson ◽  
M R Hollaway ◽  
J Beard
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Tryptic Peptide ◽  
Peptide Mapping ◽  
Thiol Group ◽  
Cysteine Residue ◽  
Amino Acid Sequences ◽  
Class I ◽  
Subunit Structure

1. The single highly reactive (class I) thiol group per 80000-mol.wt. subunit of skeletal-muscle phosphofructokinase was specifically carboxymethylated with iodo[2-14C]acetate, and after denaturation the remaining thiol groups were carboxymethylated with bromo[2-3H]acetate. After tryptic digestion and peptide ‘mapping’ it was found that the 14C radioactivity was in a spot that did not contain significant amounts of 3H radioactivity, so it is concluded that there is not a second, ‘buried’ cysteine residue within a sequence identical with that of the class-I cysteine peptide. 2. The total number of tryptic peptides as well as the number of those containing cysteine, histidine or tryptophan were inconsistent with the smallest polypeptide chain of phosphofructokinase (mol.wt. about 80000) being composed of two identical amino acid sequences. 3. The amino acid sequence of the tryptic peptide containing the class-I thiol group was shown to be Cys-Lys-Asp-Phe-Arg. This sequence is compared with part of the sequence containing the highly reactive thiol group of phosphorylase.

scholarly journals Molecular evidence that the H-2D and H-2L genes arose by duplication. Differences between the evolution of the class I genes in mice and humans.

1990 ◽  
Vol 171 (6) ◽  
pp. 2043-2061 ◽  
Author(s):  
R J Rubocki ◽  
D R Lee ◽  
W R Lie ◽  
N B Myers ◽  
T H Hansen
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Class I ◽  
Cosmid Library ◽  
Molecular Evidence ◽  
Region Gene ◽  
Sequence Comparisons ◽  
Class I Mhc ◽  
Hybridization Data ◽  
D Region

To resolve issues regarding the evolution of D region class I MHC genes and their relationship to other class I-encoding regions of the mouse, as well as man, we characterized the class I genes from the Dq region of the B10.AKM mouse strain. The Dq region was selected because it was known to express multiple gene products, yet two of the products previously characterized have structural features in common with the Ld molecule. Since DNA hybridization data defined similarities between the Dd and Dq regions, we used low-copy genomic or oligonucleotide probes derived from the Dd region of BALB/c (H-2d) to screen a B10.AKM cosmid library. Cosmid clones containing Dq, D2q, D3q, D4q, Lq, and Q1q genes have been isolated and aligned with the corresponding genes of the BALB/c MHC, thus demonstrating a similar gene organization. The two classical transplantation genes, Dq and Lq were found to be strikingly similar to each other such that exons 1-3 of Dq and Lq, are approximately 97% homologous, and exons 4-8 are identical. Furthermore, the implied amino acid sequences of both Lq and Dq molecules show considerable homology to Ld, particularly in regions presumed to be involved in ligand binding. These comparisons suggest not only that the Dq and Lq genes arose from the duplication of an Ld-like progenitor, but also that there is a selective advantage for the maintenance of an Ld-like structure. In addition, the 5' portion of the D4q gene was sequenced and found to have a 13-bp deletion and a 4-bp insertion within the alpha 2 exon. These result in a frame shift that creates a premature termination codon and potential polyadenylation site, respectively. Thus, D4q does not encode a typical class I molecule. Sequence comparisons suggest that the D4q gene did not arise from a duplication event involving an Ld-like gene such as Dq and Lq. Interestingly, the D4q molecule, if produced, would have amino acid residues in common with K and/or Q molecules that differ from those observed in D/L molecules. These findings, in conjunction with hybridization data, provide evidence that the D2, D3, and D4 genes were derived from Q genes by an unequal crossover event. Additional hybridization data using low-copy D region probes suggest that several different D region gene organizations exist among mice of different haplotypes. These and other recent molecular studies provide multiple examples of expansion and contraction of the class I genes in the D region.(ABSTRACT TRUNCATED AT 400 WORDS)

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