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The Major Histocompatibility Complex
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
It is apparent that susceptibility to certain diseases is, at least in part, a genetic trait mapping to HLA genes. Even though we usually only specify HLA class I and/or class II molecules when discussing haplotypes, there are many other genes within and close to the HLA complex (see above). Many of these genes are also polymorphic. Thus, a significant association of class I or class II specificities with a particular disorder may result from linkage with a non class I or class II gene. Such an association also does not exclude a role for environmental factors. For many HLA-linked diseases there is only a 30–70% concordance rate between monozygotic twins.
Major Histocompatibility Complex and Autoimmune Disease
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Ursula Holzer, Gerald T. Nepom
The genes for the HLA class II molecule are also clustered on chromosome 6 and code for both α and β polypeptide chains. Three letters are used to designate their loci on chromosome 6: D indicates the class, the second letter (M, O, P, Q or R) the family and the last letter (A or B) the chain α or β (Fig. 3). The single genes of the HLA genes are differentiated by Arabic numbers followed by an asterisk and then the notation of the allelic variants. For example HLA-DRB1*0101 stands for the allelic variant 0101 of the gene B1 which is a class II gene of the DR family encoding the β polypeptide chain. As of January 2001, 542 different class II alleles have been named.3
Autoimmunity in gestational diabetes mellitus
Published in Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer, Textbook of Diabetes and Pregnancy, 2018
Alberto de Leiva, Dídac Mauricio, Rosa Corcoy
Some investigators believe that patterns of HLA susceptibility in LADA patients are similar to those reported for classic DM-1, supporting the hypothesis that the genetics of autoimmune diabetes in children and adults are differentiated by only relatively few age-dependent genetic effects and the slower progression of the insulin deficiency in adults may be related to subtle variation in the HLA class II gene associations.90,91 On the contrary, other researchers have proposed that LADA patients differ genetically from classical DM-1.92,93 Two distinct monocyte gene expression clusters have been identified in autoimmune diabetes. One cluster, comprising 12 pro-inflammatory cytokine/compound genes, was detected in 60% of LADA patients and 28% of adult-onset type 1 diabetic subjects but in only 10% of juvenile-onset type 1 diabetic patients. A second cluster, comprising 10 chemotaxis, adhesion, motility, and metabolism genes, was identified in 43% of juvenile autoimmune diabetes, 33% of LADA patients, and only 9% of adult-onset type 1 diabetic individuals.92
HLA-DRB1*04:05 and HLA-DQB1*04:01: Alleles Potentially Associated with Vogt-Koyanagi-Harada in Northern Thai Patients
Published in Ocular Immunology and Inflammation, 2021
Nampeung Anukul, Kessara Pathanapitoon, Nipapan Leetrakool, Tiphakorn Guntiya, Ratsameetip Wita, Poonsub Palacajornsuk, Phennapha Klangsinsirikul
Vogt-Koyanagi-Harada (VKH) syndrome is a multi-system, autoimmune disorder commonly presenting with granulomatous panuveitis, retinal detachment, and central nervous system abnormalities, which involve human leukocyte antigen (HLA). In Thailand, the frequency of VKH disease in non-HIV-positive patients is approximately 16%,1 but to date, there has been no report on HLA alleles linked to VKH in Thai patients. However, according to previous reports, VKH is strongly associated with HLA-DR4, HLA-DR53, and HLA-DQ4 in Japanese patients.2,3 Moreover, alleles HLA-DR4, HLA-DR53, and HLA-DQ7 are identified in Chinese patients.4 Likewise, expression of the DRB1*04:05 allele was detected in 75% of Vietnamese VKH patients.5 Given the over whelming number of previous reports that suggest the HLA-class II gene family could be the primary genetic factor linked to VKH susceptibility,2–15 this study focused on genotyping HLA class II locus alleles within HLA-DRB and DQB in our three subject groups: Thai patients with VKH, other uveitis entities, and healthy blood donors. Our findings will open new insights in HLA class II-associated VKH in Northern Thailand and may help to unravel the pathogenesis of VKH with unknown etiology.
Basics of CD8 T-cell immune responses after influenza infection and vaccination with inactivated or live attenuated influenza vaccine
Published in Expert Review of Vaccines, 2018
Daniil Korenkov, Irina Isakova-Sivak, Larisa Rudenko
It is well known that HLA class I genes are expressed throughout the body, in a tissue-dependent manner [71]. A unique set of HLA class I genes determines the landscape of T cells specificities in an infected individual (MHC-restriction). In addition, an anamnestic CD8 T-cell response can be shaped by the helping or suppressing actions of CD4 T cells, which are HLA class II gene-restricted. As a result, MHC class I and II restrictions may be interconnected. Data about the specific influenza-reactive CD8 T cells arising after natural infection are limited. A few studies have analyzed the repertoire of T-cell specificities for influenza A virus infection in humans, and have found that the major fractions of influenza T-cell epitopes belong to M1 and PB1 proteins [72] or to HA and NP [73]. Although these proteins are relatively conserved across various subtypes of human and avian influenza viruses, there is evidence of selective pressure on M1 and NP CD8 T-cell epitopes in human influenza A virus [3]. In addition, the possibility of generating CD8 T-cell immune-escaped influenza virus variants in an immunocompromised patient persistently infected with influenza virus has been demonstrated [74].
HLA transgenic mice: application in reproducing idiosyncratic drug toxicity
Published in Drug Metabolism Reviews, 2020
Takeshi Susukida, Shigeki Aoki, Tomohiro Shirayanagi, Yushiro Yamada, Saki Kuwahara, Kousei Ito
On the other hand, the endogenous murine MHC class II molecule (Aβo or AEo) was deleted in most HLA class II transgenic mice in order to promote the expression of the introduced HLA class II molecules on T cells, which is a feature similar to that observed in humans (Taneja et al. 2007). The developers hypothesized that the expression of the human class II molecule, in the absence of mouse class II gene products, leads to the preferential development of a population of human class II-restricted T cells (Nabozny et al. 1996). However, it should be noted that there are disadvantages associated with MHC class II manipulation. For example, the absence of endogenous MHC class II in HLA transgenic mice (HLA–DR2 (C57BL/10), DR4 (B10.RQB3), DQ6 (B10.M), and DQ8 (B10.M)) appears to be related to the development of severe toe inflammation, resembling psoriatic arthritis, at ages of 6 months or older (Bardos et al. 2002). To avoid this issue, human-murine chimeric HLA class II constructs may be used as an alternative method to improve murine CD4+ T cell recognition. Transgenic mice expressing recombinant MHC class II molecules, in which the α2 and β2 domains are derived from mouse MHC class II and the peptide-binding α1 and β1 domains are derived from HLA counterparts (Figure 1(b)), exhibited a HLA-DR4-restricted immune response (Woods et al. 1994). Otherwise, human-murine chimeric HLA-DR4 genes, where mutations are introduced within the β2 chain at residues 110 and 139 to resemble the mouse counterpart (Figure 1(c)), are beneficial with respect to interactions with mouse CD4+ T cells (Pan et al. 1999). Indeed, this human-murine chimeric HLA-DR4 transgenic mouse line was also highly susceptible to collagen-induced arthritis upon immunization with human type II collagen (Pan et al. 1999; Taneja et al. 2003). These observations implied that either deletion of the endogenous murine MHC class II molecule or inclusion of a human-murine chimeric HLA structure would be necessary to develop a new functional HLA class II transgenic mouse model.