HLA-DR3 Molecules are the Products of an HLA Class II Immune Regulator Gene for Mycobacterium Leprae Predisposing to Tuberculoid Leprosy

1987 ◽  
pp. 101-124 ◽  
Author(s):  
Tom Ottenhoff ◽  
René De Vries
Keyword(s):  
Mycobacterium Leprae ◽  
Class Ii ◽  
Hla Class Ii ◽  
Regulator Gene ◽  
Tuberculoid Leprosy ◽  
Hla Dr3

scholarly journals HLA class II regulation and structure. Analysis with HLA-DR3 and HLA-DP point mutants.

1985 ◽  
Vol 162 (4) ◽  
pp. 1193-1207 ◽  
Author(s):  
D Pious ◽  
L Dixon ◽  
F Levine ◽  
T Cotner ◽  
R Johnson
Keyword(s):  
Cell Line ◽  
Point Mutations ◽  
Class Ii ◽  
Hla Class Ii ◽  
Mouse Strains ◽  
Parent Cell ◽  
Soluble Antigen ◽  
Mrna Levels ◽  
Site Mutation ◽  
Hla Dr3

Point mutations that affect HLA-DR structure or expression have not previously been described. In the present study, we isolated such mutants by immunoselection of an ethyl methanesulfonate-mutagenized HLA-DR3 cell line with an anti-HLA-DR3 monoclonal antibody, 16.23. To facilitate analysis, we used a parent cell line with a preexisting deletion of one haplotype encompassing DR and DQ alpha and beta. The selection yielded two sets of mutants, one with defects in DR3 structure, the other with defects in different steps leading to DR expression. Of the expression-defective mutants, one had undergone a second deletion removing the remaining DR alpha gene but no other class II genes. It had a normal abundance of DR beta mRNA but had lost binding of DR monomorphic antibodies, indicating that DR beta chains do not form noncognate dimers. A second mutant had an abnormally large DR alpha mRNA, probably resulting from a splice site mutation. Several mutants had marked reductions in DR beta mRNA levels; in two of these, the lesion appeared to be transcriptional because the reduction in DR beta mRNA was paralleled by an altered methylation pattern of one of the DR beta genes. Other expression-defective mutants had different posttranscriptional defects. Some of the mutations were similar to those that have been found in mouse strains defective in I-E expression, whereas others have no known natural counterpart. The matrix of reactivities of anti-HLA class II monomorphic antibodies with these and similar mutants allowed us to define the gene products recognized by these antibodies. A set of seven mutants were "epitope defective," that is, they expressed normal or near normal levels of HLA-DR3 but no longer bound 16.23. Unexpectedly, each of the epitope mutants had decreased DR dimer stability. These mutants should be useful in localizing the DR3 alloepitope and in elucidating its contribution as a restriction element in the presentation of soluble antigen to immune T cells.

scholarly journals Mycobacterium leprae-Specific, HLA Class II-Restricted Killing of Human Schwann Cells by CD4+Th1 Cells: A Novel Immunopathogenic Mechanism of Nerve Damage in Leprosy

2001 ◽  
Vol 166 (10) ◽  
pp. 5883-5888 ◽  
Author(s):  
Eric Spierings ◽  
Tjitske de Boer ◽  
Brigitte Wieles ◽  
Linda B. Adams ◽  
Enrico Marani ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Mycobacterium Leprae ◽  
Class Ii ◽  
Nerve Damage ◽  
Hla Class Ii ◽  
Th1 Cells

scholarly journals The Association of Myasthenia Gravis with HLA class II Antigens in Iraqi Patients

2013 ◽  
Vol 10 (1) ◽  
pp. 126-132
Author(s):  
Baghdad Science Journal
Keyword(s):  
Myasthenia Gravis ◽  
Class Ii ◽  
Hla Class Ii ◽  
Control Group ◽  
P Value ◽  
Hla Dq ◽  
Healthy Control ◽  
Hla Dr3 ◽  
Class Ii Antigens ◽  
Hla Dq2

The nature and intensity of the association of myasthenia gravis (MG) with distinct human leukocyte antigen (HLA) haplotypes differ between ethnic populations, so this study determined the association of HLA class II antigens with myasthenia gravis (MG) in Iraq.The study included Iraqi patients diagnosed with MG and two control groups the first of 54 insulin dependent diabetes mellitus patients and the second of 237 subjects as a normal control group. The test used was microlymphocytotoxicity test.The work was done in the Teaching Laboratories/Medical City/Baghdad.Results: positive associations were observed (etiological risk factors) as follows: 1. HLA-DR locus showed one positively associated allele when compared to healthy control and this was HLA-DR3 (RR: 21.05, EF0.73, & P value ? 0.05), While when compared to IDDM control no significant association appeared (since the same allele is positively associated with IDDM). 2. HLA-DQ locus showed only one positively associated allele when compared to healthy control; this was HLA-DQ2 (RR 4.67, EF 0.50, and P value ? 0.05). While no significant association appeared when compared to IDDM control. Other important clinical association were observed; association with age, gender, strong stressful events, thymoma, and other autoimmune disorders. Conclusion: The positively associated antigens which were found as follows HLA-DR3 and HLA-DQ2, while no negative association was detected.

scholarly journals GAD65 antibody prevalence and association with c-peptide, HLA class II alleles in Beninese patients with type 1 diabetes

2017 ◽  
Vol 5 (8) ◽  
pp. 3406
Author(s):  
Kaossarath A. Fagbemi ◽  
Simon Azonbakin ◽  
Marius Adjagba ◽  
Razack Osseni ◽  
Rafiath Babio ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Sensitivity And Specificity ◽  
Class Ii ◽  
Hla Class Ii ◽  
Acid Decarboxylase ◽  
C Peptide ◽  
Significant Difference ◽  
Hla Dr3 ◽  
Hla Class Ii Alleles

Background: Antibodies to glutamic acid decarboxylase and particularly their isoforms in 65 kDa are one of markers for the diagnosis of the type 1 diabetes (T1D). The aim of this study is to assess the prevalence of GAD65 antibodies (GAD65Ab) and investigate the association of GAD65Ab with C-peptide values, HLA Class II alleles genotyping. The diagnosis of T1D was set up according to American Diabetes Association criteria.Methods: Radioimmunoassay was used to determine the GAD65Ab and C-peptide values. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated as control by using the PCR-SSP method. The sensitivity and specificity of the tests were calculated by standard formula.Results: Result revealed that GAD65Ab were present in 74.5% (38/51) of the patients with T1D. There was no significant difference between the positivity or the negativity of GAD65Ab and gender, onset and duration of diabetes, frequencies of HLA-DR4, HLA-DR3-DR4, HLA-DQB1*0201. However, GAD65Ab values are linked to C-peptide concentration (χ2 =15.73, P=0.0001), the presence of HLA-DR3 (χ2 =9.75, P= 0.002), HLA-DQA1*0501 (χ2 =4.09, P= 0.043) alleles. The GAD65Ab test sensitivity and specificity were 74.5% and 94.1%, respectively. The C-peptide test showed a sensitivity around 82.4 % and 86.3 % for the specificity.Conclusions: GAD65Ab showed to be a valuable early predictive marker and is associated with the risk to develop of T1D.

scholarly journals Molecular localization and polymorphism of HLA class II restriction determinants defined by Mycobacterium leprae-reactive helper T cell clones from leprosy patients.

1986 ◽  
Vol 164 (6) ◽  
pp. 1923-1939 ◽  
Author(s):  
T H Ottenhoff ◽  
S Neuteboom ◽  
D G Elferink ◽  
R R de Vries
Keyword(s):  
Immune Response ◽  
T Cell ◽  
T Cell Activation ◽  
Mycobacterium Leprae ◽  
Class Ii ◽  
Hla Class Ii ◽  
Causative Organism ◽  
Th Cells ◽  
Cell Clones ◽  
Ir Genes

MHC class II molecules carry the restriction determinants (RDs) for antigen presentation to antigen-specific Th lymphocytes. This restriction of T cell activation endows those molecules with a key role in the induction and regulation of antigen-specific immune responses. Moreover, class II molecules are the products of class II immune response (Ir) genes. The polymorphism of these Ir genes leads to genetically controlled differences in immuneresponsiveness between different individuals. An important human example is leprosy, in which HLA class II-linked Ir genes determine the immune response against Mycobacterium leprae, the causative organism of the disease. Since the immune response against M. leprae is entirely dependent on Th cells, the HLA class II-linked Ir gene products may well regulate the immune response by controlling the presentation of M. leprae antigens to Th cells. We therefore have investigated the HLA class II RD repertoire of M. leprae-reactive Th cell clones (TLC) by means of extensive panel and inhibition studies with fully class II-typed allogeneic APCs and well-defined HLA class II-specific mAbs. The TLC studied (n, 36) proliferated specifically towards M. leprae, produced IFN-gamma upon activation, and had the CD3+CD4+CD8- phenotype. The results show in the first place that the majority of the RDs for M. leprae reside on DR and not on DP or DQ molecules. This indicates a major role for DR molecules in the immune response to M. leprae and suggests that these molecules are the main products of M. leprae-specific Ir genes. Furthermore, since the expression of DR molecules is much stronger than that of DP and DQ molecules, these findings suggest that the localization of RDs for M. leprae on class II molecules correlates with the quantitative expression of these molecules. The observation that the RDs on DR molecules coded by a DR4 haplotype were situated only on those DR molecules that are known to be highest in expression can be explained in the same way. Second, four distinct RDs related with but not identical to the Dw13 allodeterminant were carried by the DR+DRw53- (alpha beta 1) molecules of a DR4Dw13 haplotype. Since the known amino acid residue differences between the allelic DR4 related Dw beta 1 chains cannot explain the observed RD-polymorphism, this observation suggests that multiple distinct RDs unique for the DR4Dw13 haplotype are expressed by these molecules. Only 2 of 36 TLC were not restricted by DR.(ABSTRACT TRUNCATED AT 400 WORDS)

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