mhc class ii genes


Summary: Genetic loci in the vertebrate major histocompatibility complex that encode polymorphic products which control the immune response to specific antigens. The genes are found in the HLA-D region in humans and includes H-2M, I-A, and I-E loci in mice.

Top Publications

  1. El Manzalawy Y, Dobbs D, Honavar V. On evaluating MHC-II binding peptide prediction methods. PLoS ONE. 2008;3:e3268 pubmed publisher
    ..These results underscore the importance of using similarity-reduced datasets in rigorously comparing the performance of alternative MHC-II peptide prediction methods. ..
  2. Krawczyk M, Leimgruber E, Seguín Estévez Q, Dunand Sauthier I, Barras E, Reith W. Expression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genes. Nucleic Acids Res. 2007;35:595-605 pubmed thus activated by the same regulatory machinery that is known to be essential for the expression of MHC class II genes. This molecular link between the transcriptional activation of RAB4B and MHC class II genes implies that APC ..
  3. Chen Y, Zhang Y, Zhang H, Ge Y, Wan Q, Fang S. Natural selection coupled with intragenic recombination shapes diversity patterns in the major histocompatibility complex class II genes of the giant panda. J Exp Zool B Mol Dev Evol. 2010;314:208-23 pubmed publisher
    ..In this study, we investigated the genetic variations and evolutionary patterns of seven functional MHC class II genes (one DRA, two DRB, two DQA, and two DQB) of the giant panda...
  4. Yoon S, Oh H, Kim H, Hong S, Oh Y, Lee D, et al. Association of HLA class II genes with idiopathic pulmonary arterial hypertension in Koreans. Lung. 2007;185:145-9 pubmed
    ..We conclude from this study that the HLA-DRB1*0406-DQB1*0302 haplotype is associated with IPAH in Korean patients. These results suggest that certain clinical characteristics of IPAH may be controlled in part by patients' HLA alleles. ..
  5. Dionne M, Miller K, Dodson J, Caron F, Bernatchez L. Clinal variation in MHC diversity with temperature: evidence for the role of host-pathogen interaction on local adaptation in Atlantic salmon. Evolution. 2007;61:2154-64 pubmed
    ..This study illuminates the link between selection pressure from the environment, host immune adaptation, and the large-scale genetic population structure for a nonmodel vertebrate in the wild. ..
  6. Siddle H, Kreiss A, Eldridge M, Noonan E, Clarke C, Pyecroft S, et al. Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proc Natl Acad Sci U S A. 2007;104:16221-6 pubmed publisher
    ..The neoplastic clone continues to spread although the population, and, without active disease control by removal of affected animals and the isolation of disease-free animals, the Tasmanian devil faces extinction...
  7. Tollenaere C, Bryja J, Galan M, Cadet P, Deter J, Chaval Y, et al. Multiple parasites mediate balancing selection at two MHC class II genes in the fossorial water vole: insights from multivariate analyses and population genetics. J Evol Biol. 2008;21:1307-20 pubmed publisher
    We investigated the factors mediating selection acting on two MHC class II genes (DQA and DRB) in water vole (Arvicola scherman) natural populations in the French Jura Mountains...
  8. Wegner K, Kalbe M, Milinski M, Reusch T. Mortality selection during the 2003 European heat wave in three-spined sticklebacks: effects of parasites and MHC genotype. BMC Evol Biol. 2008;8:124 pubmed publisher
    ..Due to global warming the frequency of extreme climatic events is predicted to increase, which might intensify costs of parasitism and enhance selection on immune genes. ..
  9. van Oosterhout C, Joyce D, Cummings S, Blais J, Barson N, Ramnarine I, et al. Balancing selection, random genetic drift, and genetic variation at the major histocompatibility complex in two wild populations of guppies (Poecilia reticulata). Evolution. 2006;60:2562-74 pubmed
    ..Selection by parasites plays a particularly important role in the evolution of guppies in the upland habitat, which has resulted in high levels of MHC diversity being maintained in this population despite considerable genetic drift. ..

More Information


  1. Wang P, Sidney J, Dow C, Mothe B, Sette A, Peters B. A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. PLoS Comput Biol. 2008;4:e1000048 pubmed publisher
    ..We show that this consensus approach achieved best overall performance. Finally, we make the large datasets used publicly available as a benchmark to facilitate further development of MHC class II binding peptide prediction methods. ..
  2. Lata S, Bhasin M, Raghava G. Application of machine learning techniques in predicting MHC binders. Methods Mol Biol. 2007;409:201-15 pubmed publisher
    ..ANNPred allows prediction of binders for only 30 alleles purely based on the ANN. MHC2Pred is a support vector machine (SVM)-based method for prediction of promiscuous binders for 42 MHC class II alleles. ..
  3. Jinam T, Saitou N, Edo J, Mahmood A, Phipps M. Molecular analysis of HLA Class I and Class II genes in four indigenous Malaysian populations. Tissue Antigens. 2010;75:151-8 pubmed publisher
    ..These results showed the scope of HLA diversity in these indigenous minority groups and may prove beneficial for future disease association, anthropological and forensic studies. ..
  4. Aguilar A, Garza J. Patterns of historical balancing selection on the salmonid major histocompatibility complex class II beta gene. J Mol Evol. 2007;65:34-43 pubmed
    ..More than half of these sites were mammalian ABS codons, but several were not, suggesting subtle functional differences in the mammalian and teleost fish MHC molecules. ..
  5. Zhu L, Ruan X, Ge Y, Wan Q, Fang S. Low major histocompatibility complex class II DQA diversity in the Giant Panda (Ailuropoda melanoleuca). BMC Genet. 2007;8:29 pubmed
    ..Consequently, it is recommended to utilize multiple suites of microsatellite markers and multiple MHC loci to detect overall genetic variation in order to design unbiased conservation strategies. ..
  6. Rybtsova N, Leimgruber E, Seguín Estévez Q, Dunand Sauthier I, Krawczyk M, Reith W. Transcription-coupled deposition of histone modifications during MHC class II gene activation. Nucleic Acids Res. 2007;35:3431-41 pubmed
    ..These results provide strong evidence that transcription elongation can play a decisive role in the deposition of histone modification patterns associated with inducible gene activation. ..
  7. Holling T, van Eggermond M, Jager M, van den Elsen P. Epigenetic silencing of MHC2TA transcription in cancer. Biochem Pharmacol. 2006;72:1570-6 pubmed
    ..Here we discuss our current knowledge on the expression characteristics of MHC2TA and argue for an important role of epigenetic factors and mechanisms in the transcriptional silencing of MHC2TA in cancer cells. ..
  8. Dijkstra J, Katagiri T, Hosomichi K, Yanagiya K, Inoko H, Ototake M, et al. A third broad lineage of major histocompatibility complex (MHC) class I in teleost fish; MHC class II linkage and processed genes. Immunogenetics. 2007;59:305-21 pubmed publisher
    ..The present study significantly improves the knowledge of MHC class I variation in teleosts...
  9. Wright K, Ting J. Epigenetic regulation of MHC-II and CIITA genes. Trends Immunol. 2006;27:405-12 pubmed
    ..Finally, the relevance of these findings to infection, transplantation and cancer will be reviewed. ..
  10. Krawczyk M, Seguín Estévez Q, Leimgruber E, Sperisen P, Schmid C, Bucher P, et al. Identification of CIITA regulated genetic module dedicated for antigen presentation. PLoS Genet. 2008;4:e1000058 pubmed publisher
  11. Huchard E, Cowlishaw G, Raymond M, Weill M, Knapp L. Molecular study of Mhc-DRB in wild chacma baboons reveals high variability and evidence for trans-species inheritance. Immunogenetics. 2006;58:805-16 pubmed
    The MHC class II genes of many primate species were investigated extensively in recent years. However, while Mhc-DRB genes were studied in Old World monkeys such as rhesus macaques, the Mhc-DRB of baboons was only studied in a limited way...
  12. Simeon C, Fonollosa V, Tolosa C, Palou E, Selva A, Solans R, et al. Association of HLA class II genes with systemic sclerosis in Spanish patients. J Rheumatol. 2009;36:2733-6 pubmed publisher
    ..HLA alleles play a role in genetic susceptibility to SSc in Spanish patients. Some alleles are more prevalent in patients with pulmonary fibrosis and in patients with certain SSc-specific autoantibodies (anti-Topo I and ACA). ..
  13. Neff B, Garner S, Heath J, Heath D. The MHC and non-random mating in a captive population of Chinook salmon. Heredity (Edinb). 2008;101:175-85 pubmed publisher
    ..These results indicate that sexual selection favours increased body size and perhaps integument coloration in males as well as increases genetic diversity at the MHC by female mate choice. ..
  14. Blais J, Rico C, van Oosterhout C, Cable J, Turner G, Bernatchez L. MHC adaptive divergence between closely related and sympatric African cichlids. PLoS ONE. 2007;2:e734 pubmed
    ..We tested the hypothesis that these species have undergone divergent selection at MHC class II genes, which are known to contribute to olfactory-based mate choice in other taxa.
  15. Worley K, Gillingham M, Jensen P, Kennedy L, Pizzari T, Kaufman J, et al. Single locus typing of MHC class I and class II B loci in a population of red jungle fowl. Immunogenetics. 2008;60:233-47 pubmed publisher
    ..This is the first time that a population of red jungle fowl has been typed at the MHC region, laying the basis for further research into the underlying processes acting to maintain MHC diversity in this and other species. ..
  16. Meyer Lucht Y, Sommer S. MHC diversity and the association to nematode parasitism in the yellow-necked mouse (Apodemus flavicollis). Mol Ecol. 2005;14:2233-43 pubmed
    ..In contrast, the allele Apfl-DRB*23 showed a significant association to low FEC of the most common nematode. Thus, our results provide evidence for pathogen-driven selection acting through rare allele advantage under natural conditions. ..
  17. Cui J, Han L, Lin H, Zhang H, Tang Z, Zheng C, et al. Prediction of MHC-binding peptides of flexible lengths from sequence-derived structural and physicochemical properties. Mol Immunol. 2007;44:866-77 pubmed
    ..01-5% for 24 and 5-8% for 6 alleles) of its constituent peptides are predicted as binders. Our software can be accessed at . ..
  18. Gomez J, Majumder P, Nagarajan U, Boss J. X box-like sequences in the MHC class II region maintain regulatory function. J Immunol. 2005;175:1030-40 pubmed
  19. Zika E, Fauquier L, Vandel L, Ting J. Interplay among coactivator-associated arginine methyltransferase 1, CBP, and CIITA in IFN-gamma-inducible MHC-II gene expression. Proc Natl Acad Sci U S A. 2005;102:16321-6 pubmed
    ..These results suggest functional and temporal relationships among CIITA, CARM1, and CBP for IFN-gamma induction of MHC-II. ..
  20. Gialitakis M, Kretsovali A, Spilianakis C, Kravariti L, Mages J, Hoffmann R, et al. Coordinated changes of histone modifications and HDAC mobilization regulate the induction of MHC class II genes by Trichostatin A. Nucleic Acids Res. 2006;34:765-72 pubmed
    ..A complex pattern of gene reprogramming by TSA involves immune recognition, antiviral, apoptotic and inflammatory pathways and extends the rationale for using Histone Deacetylase Inhibitors (HDACi) to modulate the immune response. ..
  21. Wegner K, Kalbe M, Rauch G, Kurtz J, Schaschl H, Reusch T. Genetic variation in MHC class II expression and interactions with MHC sequence polymorphism in three-spined sticklebacks. Mol Ecol. 2006;15:1153-64 pubmed
    ..The observed differences among families and the negative correlation with individual sequence diversity imply that MHC expression is evolutionary relevant for the onset and control of the immune response in natural populations. ..
  22. Bontrop R. Comparative genetics of MHC polymorphisms in different primate species: duplications and deletions. Hum Immunol. 2006;67:388-97 pubmed
    ..The human HLA system represents the most thoroughly investigated MHC of any contemporary living primate species, and so it will serve as a reference. ..
  23. Lochamy J, Rogers E, Boss J. CREB and phospho-CREB interact with RFX5 and CIITA to regulate MHC class II genes. Mol Immunol. 2007;44:837-47 pubmed
    ..Together, these data provide genetic and biochemical evidence of the specific associations between CREB and two elements of the MHC-II regulatory complex and of the role played by phosphorylated CREB at MHC-II promoters. ..
  24. Baquero J, Miranda S, Murillo O, Mateus H, Trujillo E, Suarez C, et al. Reference strand conformational analysis (RSCA) is a valuable tool in identifying MHC-DRB sequences in three species of Aotus monkeys. Immunogenetics. 2006;58:590-7 pubmed publisher
  25. Oliver M, Piertney S. Isolation and characterization of a MHC class II DRB locus in the European water vole (Arvicola terrestris). Immunogenetics. 2006;58:390-5 pubmed
  26. Nath S, Kales S, Fujiki K, Dixon B. Major histocompatibility class II genes in rainbow trout (Oncorhynchus mykiss) exhibit temperature dependent downregulation. Immunogenetics. 2006;58:443-53 pubmed
  27. Gouin N, Deakin J, Miska K, Miller R, Kammerer C, Graves J, et al. Linkage mapping and physical localization of the major histocompatibility complex region of the marsupial Monodelphis domestica. Cytogenet Genome Res. 2006;112:277-85 pubmed publisher
    ..Family based linkage analyses of two M. domestica MHC Class I genes (UA1, UG) and three MHC Class II genes (DAB, DMA, and DMB) revealed that these genes were tightly linked and positioned in the central region of ..
  28. Doxiadis G, Rouweler A, de Groot N, Louwerse A, Otting N, Verschoor E, et al. Extensive sharing of MHC class II alleles between rhesus and cynomolgus macaques. Immunogenetics. 2006;58:259-68 pubmed
    ..Despite extensive allele sharing, rhesus and cynomolgus monkeys do not appear to possess identical Mhc class II haplotypes, thus illustrating that new haplotypes were generated after speciation by recombination-like processes. ..
  29. Bryja J, Galan M, Charbonnel N, Cosson J. Duplication, balancing selection and trans-species evolution explain the high levels of polymorphism of the DQA MHC class II gene in voles (Arvicolinae). Immunogenetics. 2006;58:191-202 pubmed
    ..We discuss possible role of parasites in forming the recent polymorphism pattern of the DQA locus in voles. ..
  30. Su rez C, Patarroyo M, Trujillo E, Estupi n M, Baquero J, Parra C, et al. Owl monkey MHC-DRB exon 2 reveals high similarity with several HLA-DRB lineages. Immunogenetics. 2006;58:542-58 pubmed publisher
    ..These observations concerning previous findings of similarity between the Aotus immune system molecules and their human counterparts affirm this specie's usefulness as an excellent animal model in biomedical research...
  31. Babik W, Durka W, Radwan J. Sequence diversity of the MHC DRB gene in the Eurasian beaver (Castor fiber). Mol Ecol. 2005;14:4249-57 pubmed
    ..Current MHC monomorphism in the majority of populations may be the result of the superimposition of the recent bottleneck on pre-existing genetic structure resulting from population subdivision and differential pathogen pressure. ..
  32. Miller H, Belov K, Daugherty C. Characterization of MHC class II genes from an ancient reptile lineage, Sphenodon (tuatara). Immunogenetics. 2005;57:883-91 pubmed
    ..The tuatara sequences do not strongly group with other reptile sequences on a phylogenetic tree, reflecting the antiquity of the Sphenodon lineage and the lack of closely related sequences for comparison. ..
  33. Abbott K, Wickings E, Knapp L. High levels of diversity characterize mandrill (Mandrillus sphinx) Mhc-DRB sequences. Immunogenetics. 2006;58:628-40 pubmed
    ..As observed in other primates, some new lineages may have arisen through the process of gene conversion. These findings indicate that mandrills have Mhc-DRB diversity not unlike rhesus macaques and humans...
  34. Reith W, LeibundGut Landmann S, Waldburger J. Regulation of MHC class II gene expression by the class II transactivator. Nat Rev Immunol. 2005;5:793-806 pubmed
  35. Reusch T, Langefors A. Inter- and intralocus recombination drive MHC class IIB gene diversification in a teleost, the three-spined stickleback Gasterosteus aculeatus. J Mol Evol. 2005;61:531-41 pubmed
    ..Nonindependence of molecular evolution across loci and frequent recombination suggest that MHC class II genes of bony fish may follow different evolutionary dynamics than those of mammals...
  36. Yang X, Cai S, Zhang W, Tang X, Shin H, Lee J, et al. Semi-vioxanthin isolated from marine-derived fungus regulates tumor necrosis factor-alpha, cluster of differentiation (CD) 80, CD86, and major histocompatibility complex class II expression in RAW264.7 cells via nuclear factor-kappaB and mitogen-acti. Biol Pharm Bull. 2008;31:2228-33 pubmed
    ..Activation of NF-kappaB and ERK1/2 were necessary for CD80, CD86 and MHCII expression induced by semi-vioxanthin. These data suggest that semi-vioxanthin has immunoregulatory effects. ..
  37. Iliopoulou B, Alroy J, Huber B. Persistent arthritis in Borrelia burgdorferi-infected HLA-DR4-positive CD28-negative mice post-antibiotic treatment. Arthritis Rheum. 2008;58:3892-901 pubmed publisher
    ..The establishment of this murine model allows, for the first time, the elucidation of the immunologic events that lead to persistent Lyme arthritis post-antibiotic therapy in genetically susceptible individuals. ..
  38. Mausberg A, Jander S, Reichmann G. Intracerebral granulocyte-macrophage colony-stimulating factor induces functionally competent dendritic cells in the mouse brain. Glia. 2009;57:1341-50 pubmed publisher
    ..Moreover, these GM-CSF-induced DC display an activated phenotype and exhibit the capacity to act as fully competent DC even without a further inflammatory stimulus. ..
  39. Dalva K, Beksac M. Sequence-specific primed PCR (PCR-SSP) typing of HLA Class I and Class II alleles. Methods Mol Med. 2007;134:51-60 pubmed
    ..However, this technique is limited by the number of the samples that can be processed at one time and also by the number of the primer mixes that can be utilized. ..
  40. Tripathy A, Shankarkumar U, Chadha M, Ghosh K, Arankalle V. Association of HLA alleles with hepatitis C infection in Maharashtra, western India. Indian J Med Res. 2009;130:550-5 pubmed
    ..64, OR=5.16, P=0.0001) was significantly increased among HCV infected individuals. Our data suggest that among the western Indian population, certain HLA alleles or associated haplotype influence HCV infection as a host genetic factor. ..
  41. Fuentes Mattei E, Rivera E, Gioda A, Sanchez Rivera D, Roman Velazquez F, Jimenez Velez B. Use of human bronchial epithelial cells (BEAS-2B) to study immunological markers resulting from exposure to PM(2.5) organic extract from Puerto Rico. Toxicol Appl Pharmacol. 2010;243:381-9 pubmed publisher
    ..This research provides a new insight into the effects of PM(2.5) organic fractions on specific effectors and their possible role in the development of respiratory inflammatory diseases in Puerto Rico. ..
  42. Larruskain A, Minguij n E, Garc a Etxebarria K, Moreno B, Arostegui I, Juste R, et al. MHC class II DRB1 gene polymorphism in the pathogenesis of Maedi-Visna and pulmonary adenocarcinoma viral diseases in sheep. Immunogenetics. 2010;62:75-83 pubmed publisher
    ..This is the first study demonstrating significant associations between sheep Mhc-DRB1 alleles and susceptibility to OPA and Maedi. Therefore, both diseases are suitable candidates for more comprehensive genetic studies...
  43. Hoek A, Rutten V, van der Zee R, Davies C, Koets A. Epitopes of Mycobacterium avium ssp. paratuberculosis 70kDa heat-shock protein activate bovine helper T cells in outbred cattle. Vaccine. 2010;28:5910-9 pubmed publisher
    ..These findings indicate the potential of the MAP Hsp70 subunit vaccine as a tool to control paratuberculosis in outbred cattle populations. ..
  44. Chuang T, Lee S, Liao K, Hsiao Y, Lo C, Chiang B, et al. Electroporation-mediated IL-12 gene therapy in a transplantable canine cancer model. Int J Cancer. 2009;125:698-707 pubmed publisher
    ..The results also indicate that CTVT is an excellent large animal cancer model for testing immunogene therapies mediated by electroporation...
  45. Bagley J, Paez Cortez J, Tian C, Iacomini J. Gene therapy in type 1 diabetes. Crit Rev Immunol. 2008;28:301-24 pubmed
    ..We review these studies here. ..
  46. Meissner M, Whiteside T, Kaufmann R, Seliger B. CIITA versus IFN-gamma induced MHC class II expression in head and neck cancer cells. Arch Dermatol Res. 2009;301:189-93 pubmed publisher
    ..These findings may have a significant impact on practical and clinical aspects of tumor immunotherapeutic strategies. ..
  47. Wang M, Windgassen D, Papoutsakis E. Comparative analysis of transcriptional profiling of CD3+, CD4+ and CD8+ T cells identifies novel immune response players in T-cell activation. BMC Genomics. 2008;9:225 pubmed publisher
    ..Significantly, it made possible to identify the temporal patterns of many previously known T-cell activation genes, and also identify genes implicated in effector functions of and communication between CD4+ and CD8+ T cells. ..
  48. Gao D, Mondal T, Lawrence D. Lead effects on development and function of bone marrow-derived dendritic cells promote Th2 immune responses. Toxicol Appl Pharmacol. 2007;222:69-79 pubmed
  49. Hauswaldt J, Stuckas H, Pfautsch S, Tiedemann R. Molecular characterization of MHC class II in a nonmodel anuran species, the fire-bellied toad Bombina bombina. Immunogenetics. 2007;59:479-91 pubmed
    ..With our new beta1 primers, we were able to generate sequences in other species of anurans. We provide here a first phylogenetic analysis of this gene in amphibians. ..
  50. Schaschl H, Wegner K. Contrasting mode of evolution between the MHC class I genomic region and class II region in the three-spined stickleback (Gasterosteus aculeatus L.; Gasterosteidae: Teleostei). Immunogenetics. 2007;59:295-304 pubmed
    ..In humans, however, homologues of Oct-2 beta and ATPasealpha3 lie outside the MHC region, which indicates that the concentration of immune genes found in mammalian genomes is a derived state...
  51. Ota M, Katsuyama Y, Hamano H, Umemura T, Kimura A, Yoshizawa K, et al. Two critical genes (HLA-DRB1 and ABCF1)in the HLA region are associated with the susceptibility to autoimmune pancreatitis. Immunogenetics. 2007;59:45-52 pubmed
    ..The two critical HLA regions for susceptibility to AIP are limited to the HLA-DRB1*0405-DQB1*0401 in the class II and the ABCF1 proximal to C3-2-11, telomeric of HLA-E, in the class I regions...
  52. Siala M, Mahfoudh N, Fourati H, Gdoura R, Younes M, Kammoun A, et al. MHC class I and class II genes in Tunisian patients with reactive and undifferentiated arthritis. Clin Exp Rheumatol. 2009;27:208-13 pubmed
    ..Our results also suggested that some of the additional HLA antigens were associated with ReA including HLA-B51 and HLA-DRB1*04 alleles. UA seemed to have a genetic background different from ReA in Tunisian patients. ..
  53. Brignone C, Escudier B, Grygar C, Marcu M, Triebel F. A phase I pharmacokinetic and biological correlative study of IMP321, a novel MHC class II agonist, in patients with advanced renal cell carcinoma. Clin Cancer Res. 2009;15:6225-31 pubmed publisher
    ..015). The absence of toxicity and the demonstration of activity at doses above 6 mg warrant further disease-directed studies of IMP321 in combined regimens (e.g., chemoimmunotherapy). ..