Genomes and Genes
Gene Symbol: H2-Ab1
Description: histocompatibility 2, class II antigen A, beta 1
Alias: AI845868, Abeta, H-2Ab, H2-Ab, I-Abeta, IAb, Ia-2, Ia2, Rmcs1, histocompatibility 2, class II antigen A, beta 1, H-2 class II histocompatibility antigen, A beta chain, MHC class II H2-IA-beta-psi, MHC class II antigen A beta, major histocompatibility complex class II beta chain, response to metastatic cancers 1
- Pacholczyk R, Kern J, Singh N, Iwashima M, Kraj P, Ignatowicz L. Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. Immunity. 2007;27:493-504 pubmed..Our results show that high-affinity, autoreactive TCRs are rare on all CD4+ T cells and suggest that selecting self-peptide is different from the peptide that activates the same regulatory T cells in the periphery. ..
- Burchill M, Yang J, Vogtenhuber C, Blazar B, Farrar M. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol. 2007;178:280-90 pubmed..Finally, STAT5 binds to the promoter of the foxp3 gene suggesting that IL-2Rbeta-dependent STAT5 activation promotes Treg differentiation by regulating expression of foxp3. ..
- Hashimoto K, Joshi S, Koni P. A conditional null allele of the major histocompatibility IA-beta chain gene. Genesis. 2002;32:152-3 pubmed
- Zou Y, Sunshine M, Taniuchi I, Hatam F, Killeen N, Littman D. Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage. Nat Genet. 2001;29:332-6 pubmed..The epigenetic inheritance of the silenced CD4 locus was not affected by the inhibition of DNA methylation or histone deacetylation, and may thus involve other mechanisms that ensure a stable state of gene expression. ..
- Coles M, Raulet D. NK1.1+ T cells in the liver arise in the thymus and are selected by interactions with class I molecules on CD4+CD8+ cells. J Immunol. 2000;164:2412-8 pubmed..1+ T cells or are induced to proliferate after having left the thymus. The results indicate that NK1.1+ T cells, like conventional T cells, arise in the thymus where they are selected by interactions with restricting molecules. ..
- Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, Ogasawara K. Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells. Proc Natl Acad Sci U S A. 2011;108:18360-5 pubmed publisher..These results suggest that MHCII-dressed NK cells generated through NK-DC interactions regulate T cell-mediated immune responses. ..
- Cheng S, Smart M, Hanson J, David C. Characterization of HLA DR2 and DQ8 transgenic mouse with a new engineered mouse class II deletion, which lacks all endogenous class II genes. J Autoimmun. 2003;21:195-9 pubmed..However, these mice carry the functional mouse Eb gene from the Abeta(0/0) construct and could express Ebeta/DRalpha(Ealpha) molecules and shape the T cell repertoire in these mice...
- Egawa T, Tillman R, Naoe Y, Taniuchi I, Littman D. The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J Exp Med. 2007;204:1945-57 pubmed..These results indicate that Runx proteins have important roles at multiple stages of T cell development and in the homeostasis of mature T cells. ..
- Setoguchi R, Tachibana M, Naoe Y, Muroi S, Akiyama K, Tezuka C, et al. Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development. Science. 2008;319:822-5 pubmed publisher..Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system. ..
- Darrasse Jèze G, Deroubaix S, Mouquet H, Victora G, Eisenreich T, Yao K, et al. Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J Exp Med. 2009;206:1853-62 pubmed publisher..The increase in T reg cells induced by DC expansion is sufficient to prevent type 1 autoimmune diabetes and IBD, which suggests that interference with this feedback loop will create new opportunities for immune-based therapies. ..
- Maurice D, Hooper J, Lang G, Weston K. c-Myb regulates lineage choice in developing thymocytes via its target gene Gata3. EMBO J. 2007;26:3629-40 pubmed..We show that Gata3 is a direct target of c-Myb, and propose that c-Myb is an important regulator of Gata3, required for transduction of the T-cell receptor signal for subsequent helper cell lineage differentiation. ..
- Muroi S, Naoe Y, Miyamoto C, Akiyama K, Ikawa T, Masuda K, et al. Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate. Nat Immunol. 2008;9:1113-21 pubmed publisher..Our results show how an initial lineage-specification signal can be amplified and stabilized during the lineage-commitment process. ..
- Haks M, Belkowski S, Ciofani M, Rhodes M, Lefebvre J, Trop S, et al. Low activation threshold as a mechanism for ligand-independent signaling in pre-T cells. J Immunol. 2003;170:2853-61 pubmed..Taken together these data suggest that cell-autonomous, ligand-independent signaling is primarily a property of the thymocytes in which pre-TCR signaling occurs. ..
- Moran A, Holzapfel K, Xing Y, Cunningham N, Maltzman J, Punt J, et al. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J Exp Med. 2011;208:1279-89 pubmed publisher..However, although T(reg) cells continued to perceive strong TCR signals in the periphery, iNKT cells did not. Finally, we show that T(reg) cell progenitors compete for recognition of rare stimulatory TCR self-ligands. ..
- Pope C, Kim S, Marzo A, Masopust D, Williams K, Jiang J, et al. Organ-specific regulation of the CD8 T cell response to Listeria monocytogenes infection. J Immunol. 2001;166:3402-9 pubmed..Overall, the results point to novel pathways of tissue-specific regulation of primary and memory antimicrobial CD8 T cell responses. ..
- Benlagha K, Wei D, Veiga J, Teyton L, Bendelac A. Characterization of the early stages of thymic NKT cell development. J Exp Med. 2005;202:485-92 pubmed..1neg CD4 cells. These findings identify the HSAhigh CD4+ stage as a potential branchpoint between NKT and conventional T lineages and between the CD4 and DN NKT sublineages. ..
- Madsen L, Labrecque N, Engberg J, Dierich A, Svejgaard A, Benoist C, et al. Mice lacking all conventional MHC class II genes. Proc Natl Acad Sci U S A. 1999;96:10338-43 pubmed..These mice feature immune system perturbations like those of Aalpha and Abeta knockout animals, notably a dearth of CD4(+) lymphocytes in the thymus and spleen...
- Shin J, Ebersold M, Pypaert M, Delamarre L, Hartley A, Mellman I. Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination. Nature. 2006;444:115-8 pubmed..Dendritic cells thus exhibit a unique ability to regulate MHC II surface expression by selectively controlling MHC II ubiquitination. ..
- Johnson S, Zhan Y, Sutherland R, Mount A, Bedoui S, Brady J, et al. Selected Toll-like receptor ligands and viruses promote helper-independent cytotoxic T cell priming by upregulating CD40L on dendritic cells. Immunity. 2009;30:218-27 pubmed publisher..Thus, CD40L upregulation on DCs promoted optimal priming of CD8(+) T cells without CD4(+) T cells, providing a mechanism by which pathogens may elicit helper-independent CTL immunity. ..
- Swee L, Bosco N, Malissen B, Ceredig R, Rolink A. Expansion of peripheral naturally occurring T regulatory cells by Fms-like tyrosine kinase 3 ligand treatment. Blood. 2009;113:6277-87 pubmed publisher..It also reinforces the relevance of FLT3L treatment in GVHD by its ability to increase both the number of tolerizing DCs and NTregs. ..
- Ohmura Hoshino M, Matsuki Y, Mito Yoshida M, Goto E, Aoki Kawasumi M, Nakayama M, et al. Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells. J Immunol. 2009;183:6893-7 pubmed publisher..These results suggest that the accumulation of MHC II resulting from loss of ubiquitination caused cDC abnormality; therefore, MARCH-I may function as a housekeeper of cDC in the steady state. ..
- Nasreen M, Ueno T, Saito F, Takahama Y. In vivo treatment of class II MHC-deficient mice with anti-TCR antibody restores the generation of circulating CD4 T cells and optimal architecture of thymic medulla. J Immunol. 2003;171:3394-400 pubmed
- Black K, Murray J, David C. HLA-DQ determines the response to exogenous wheat proteins: a model of gluten sensitivity in transgenic knockout mice. J Immunol. 2002;169:5595-600 pubmed..These data suggest that this HLA class II transgenic murine model of gluten sensitivity may provide insight into the initiation of the MHC class II-restricted gluten sensitivity in celiac disease. ..
- Sarafova S, Erman B, Yu Q, Van Laethem F, Guinter T, Sharrow S, et al. Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR/coreceptor specificity. Immunity. 2005;23:75-87 pubmed..This study demonstrates that termination of coreceptor transcription during positive selection promotes CD8-lineage fate, regardless of TCR specificity or coreceptor protein identity. ..
- Egawa T, Littman D. ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage. Nat Immunol. 2008;9:1131-9 pubmed publisher..Our results suggest that MHC class II-selected thymocytes are directed toward the CD4(+) lineage independently of ThPOK but require ThPOK to prevent Runx-dependent differentiation toward the CD8(+) lineage. ..
- Dougan S, Ashour J, Karssemeijer R, Popp M, Avalos A, Barisa M, et al. Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus. Nature. 2013;503:406-9 pubmed publisher..We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response. ..
- Shedlock D, Whitmire J, Tan J, MacDonald A, Ahmed R, Shen H. Role of CD4 T cell help and costimulation in CD8 T cell responses during Listeria monocytogenes infection. J Immunol. 2003;170:2053-63 pubmed
- Park S, Weiss A, Benlagha K, Kyin T, Teyton L, Bendelac A. The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families. J Exp Med. 2001;193:893-904 pubmed..Altogether, these findings imply that lipid recognition by CD1d-restricted T cells may have largely evolved as an innate rather than an adaptive arm of the mouse immune system. ..
- Zhu Y, Rudensky A, Corper A, Teyton L, Wilson I. Crystal structure of MHC class II I-Ab in complex with a human CLIP peptide: prediction of an I-Ab peptide-binding motif. J Mol Biol. 2003;326:1157-74 pubmed..In addition, after examining the published sequences of peptides presented by I-A(b), we discuss the possibility of predicting peptide alignment in the I-A(b) binding groove using a simple scoring matrix. ..
- Martin B, Bourgeois C, Dautigny N, Lucas B. On the role of MHC class II molecules in the survival and lymphopenia-induced proliferation of peripheral CD4+ T cells. Proc Natl Acad Sci U S A. 2003;100:6021-6 pubmed..Nevertheless, interactions with classical MHC class II molecules are required for CD4(+) T cells to survive in CD8(+) T-cell-containing mice. ..
- Boes M, Cerny J, Massol R, Op den Brouw M, Kirchhausen T, Chen J, et al. T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature. 2002;418:983-8 pubmed..We propose that such tubulation serves to facilitate the ensuing T-cell response. ..
- Shimoda M, Mmanywa F, Joshi S, Li T, Miyake K, Pihkala J, et al. Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance. J Immunol. 2006;176:6503-11 pubmed..Thus, our findings lend support to the proposal that Treg cell homeostasis depends on a delicate balance with a population of self-reactive IL-2-producing CD4+CD25+ cells which are themselves at least in part MHC-II-dependent. ..
- Hinterberger M, Aichinger M, Prazeres da Costa O, Voehringer D, Hoffmann R, Klein L. Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance. Nat Immunol. 2010;11:512-9 pubmed publisher..Our data document an autonomous contribution of mTECs to both dominant and recessive mechanisms of CD4(+) T cell tolerance and support an avidity model of T(reg) cell development versus deletion. ..
- Lemos M, Fan L, Lo D, Laufer T. CD8alpha+ and CD11b+ dendritic cell-restricted MHC class II controls Th1 CD4+ T cell immunity. J Immunol. 2003;171:5077-84 pubmed..These findings indicate that DCs are not only key initiators of the primary response, but provide all of the necessary cognate interactions to control CD4(+) T cell fate during the primary immune response. ..
- He X, Park K, Wang H, He X, Zhang Y, Hua X, et al. CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus. Immunity. 2008;28:346-58 pubmed publisher..We propose a silencer-dependent model of lineage choice, whereby inactivation of the DRE silencer by a strong TCR signal leads to CD4 commitment, whereas continued silencer activity leads to CD8 commitment. ..
- Fowlkes B, Robey E. A reassessment of the effect of activated Notch1 on CD4 and CD8 T cell development. J Immunol. 2002;169:1817-21 pubmed..We suggest that the discrepancies in previous reports of Notch1IC transgenic mice are due to differences in the propensity of the two different transgenic lines to develop tumors. ..
- Sakaguchi S, Hombauer M, Bilic I, Naoe Y, Schebesta A, Taniuchi I, et al. The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes. Nat Immunol. 2010;11:442-8 pubmed publisher..MAZR bound the silencer of the gene encoding Th-POK, which indicated direct regulation of this locus by MAZR. Thus, MAZR is part of the transcription factor network that regulates the CD8 lineage differentiation of DP thymocytes. ..
- Keefe R, Dave V, Allman D, Wiest D, Kappes D. Regulation of lineage commitment distinct from positive selection. Science. 1999;286:1149-53 pubmed..However, neither TCR-mediated signaling nor positive selection is impaired. Thus, the HD mutation provides genetic evidence that lineage commitment may be mechanistically distinct from positive selection. ..
- Kish D, Gorbachev A, Fairchild R. Regulatory function of CD4+CD25+ T cells from Class II MHC-deficient mice in contact hypersensitivity responses. J Leukoc Biol. 2007;82:85-92 pubmed..These results identify functional CD4+CD25+ Treg in Class II MHC-/- mice, which restrict hapten-specific CD8+ T cell priming and the magnitude of CHS responses. ..
- Subramanian S, Yim Y, Liu K, Tus K, Zhou X, Wakeland E. Epistatic suppression of systemic lupus erythematosus: fine mapping of Sles1 to less than 1 mb. J Immunol. 2005;175:1062-72 pubmed..Sle1 Sles1)F(1)s. These findings localize and characterize the suppressive properties of Sles1 and implicate 129 as a useful strain for aiding in the identification of this elusive epistatic modifier gene. ..
- Saint Mezard P, Chavagnac C, Vocanson M, Kehren J, Rozieres A, Bosset S, et al. Deficient contact hypersensitivity reaction in CD4-/- mice is because of impaired hapten-specific CD8+ T cell functions. J Invest Dermatol. 2005;124:562-9 pubmed
- Lemos M, Esquivel F, Scott P, Laufer T. MHC class II expression restricted to CD8alpha+ and CD11b+ dendritic cells is sufficient for control of Leishmania major. J Exp Med. 2004;199:725-30 pubmed..major infection using a mouse model in which MHC II, I-Abeta(b), expression is restricted to CD11b+ and CD8alpha+ dendritic cells (DCs)...
- Kovats S, Grubin C, Eastman S, deRoos P, Dongre A, van Kaer L, et al. Invariant chain-independent function of H-2M in the formation of endogenous peptide-major histocompatibility complex class II complexes in vivo. J Exp Med. 1998;187:245-51 pubmed..These findings are consistent with the idea that H-2M functions as a chaperone in the peptide loading of class II molecules in vivo. ..
- Katz J, Benoist C, Mathis D. Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice. Eur J Immunol. 1993;23:3358-60 pubmed..We question this interpretation because NOD mice lacking MHC class I molecules, hence CD8+ T cells, do not display even insulitis when expected. ..
- Grusby M, Johnson R, Papaioannou V, Glimcher L. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991;253:1417-20 pubmed..These results provide genetic evidence that class II molecules are required for the maturation and function of mature CD4+ T cells. ..
- Buhlmann J, Foy T, Aruffo A, Crassi K, Ledbetter J, Green W, et al. In the absence of a CD40 signal, B cells are tolerogenic. Immunity. 1995;2:645-53 pubmed..These studies provide insights into the tolerogenic capacity of resting B cells and outlines a practical approach to exploit this function. ..
- Lindstedt R, Liljedahl M, Peleraux A, Peterson P, Karlsson L. The MHC class II molecule H2-M is targeted to an endosomal compartment by a tyrosine-based targeting motif. Immunity. 1995;3:561-72 pubmed..Thus, the targeting motif of H2-M appears to be supplementary, rather than essential for class II-peptide association. ..
- Chakkalath H, Theodos C, Markowitz J, Grusby M, Glimcher L, Titus R. Class II major histocompatibility complex-deficient mice initially control an infection with Leishmania major but succumb to the disease. J Infect Dis. 1995;171:1302-8 pubmed..major and that in the absence of these cells and molecules, such mice can transiently control infection with L. major but are unable to resolve such infections. ..
- Grusby M, Auchincloss H, Lee R, Johnson R, Spencer J, Zijlstra M, et al. Mice lacking major histocompatibility complex class I and class II molecules. Proc Natl Acad Sci U S A. 1993;90:3913-7 pubmed..Taken together, these results emphasize the plasticity of the immune system and suggest that MHC-deficient mice may be useful for examining compensatory mechanisms in severely immunocompromised animals. ..
- Cosgrove D, Gray D, Dierich A, Kaufman J, LeMeur M, Benoist C, et al. Mice lacking MHC class II molecules. Cell. 1991;66:1051-66 pubmed..In short, the class II-negative mice have confirmed some old ideas about lymphocyte differentiation, but have provided some surprises. ..
- Ito K, Bian H, Molina M, Han J, Magram J, Saar E, et al. HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis. J Exp Med. 1996;183:2635-44 pubmed..Non-Tg mice immunized with either PLP175-192 or MBP87-106 did not develop EAE. These results demonstrated that a human MHC class II binding site alone can confer susceptibility to an experimentally induced murine autoimmune disease. ..
- Dave V, Allman D, Keefe R, Hardy R, Kappes D. HD mice: a novel mouse mutant with a specific defect in the generation of CD4(+) T cells. Proc Natl Acad Sci U S A. 1998;95:8187-92 pubmed..This is the first genetic defect of its kind to be described in the mouse and may prove highly informative in understanding the molecular pathways underlying lineage commitment. ..
- Suzuki H, Punt J, Granger L, Singer A. Asymmetric signaling requirements for thymocyte commitment to the CD4+ versus CD8+ T cell lineages: a new perspective on thymic commitment and selection. Immunity. 1995;2:413-25 pubmed..These results are incompatible with current concepts and require a new perspective on lineage commitment and positive selection, which we refer to as asymmetric commitment. ..
- McKenzie I, Morgan G, Sandrin M, Michaelides M, Melvold R, Kohn H. B6.C-H-2bm12. A new H-2 mutation in the I region in the mouse. J Exp Med. 1979;150:1323-38 pubmed..Serological analysis with a battery of H-2b, Iab, and other Ia sera, both by cytotoxicity, rosetting, and also by absorption analysis, indicated no alteration in H-..
- Ignatowicz L, Kappler J, Marrack P. The repertoire of T cells shaped by a single MHC/peptide ligand. Cell. 1996;84:521-9 pubmed..T cells that mature in thymuses expressing a single MHC/peptide ligand react frequently with foreign MHC, suggesting that the repertoire of alpha beta receptors may be more biased toward reaction with MHC than was previously thought. ..
- Dautigny N, Le Campion A, Lucas B. Timing and casting for actors of thymic negative selection. J Immunol. 1999;162:1294-302 pubmed..Finally, we show involvement in opposing directions for p59fyn and SHP-1 molecules in signaling for thymic negative selection. ..
- Fung Leung W, Surh C, Liljedahl M, Pang J, Leturcq D, Peterson P, et al. Antigen presentation and T cell development in H2-M-deficient mice. Science. 1996;271:1278-81 pubmed..Their CD4+ cells were unresponsive to self H2-M-deficient antigen-presenting cells (APCs) but were hyperreactive to wild-type APCs. H2-M-deficient APCs failed to elicit proliferative responses from wild-type T cells. ..
- Liu J, Purdy L, Rabinovitch S, Jevnikar A, Elliott J. Major DQ8-restricted T-cell epitopes for human GAD65 mapped using human CD4, DQA1*0301, DQB1*0302 transgenic IA(null) NOD mice. Diabetes. 1999;48:469-77 pubmed
- Mendiratta S, Kovalik J, Hong S, Singh N, Martin W, van Kaer L. Peptide dependency of alloreactive CD4+ T cell responses. Int Immunol. 1999;11:351-60 pubmed..APC from these mice were used as targets and stimulators for alloreactive CD4+ T cells. Results demonstrated that the vast majority of CD4+ alloreactive T cells recognize MHC class II molecules in a peptide-dependent fashion. ..
- Chan S, Cosgrove D, Waltzinger C, Benoist C, Mathis D. Another view of the selective model of thymocyte selection. Cell. 1993;73:225-36 pubmed
- Chan S, Correia Neves M, Dierich A, Benoist C, Mathis D. Visualization of CD4/CD8 T cell commitment. J Exp Med. 1998;188:2321-33 pubmed..Finally, we found no evidence of a CD4 default pathway. ..
- Miyazaki T, Wolf P, Tourne S, Waltzinger C, Dierich A, Barois N, et al. Mice lacking H2-M complexes, enigmatic elements of the MHC class II peptide-loading pathway. Cell. 1996;84:531-41 pubmed..Peripheral T cells reacted strongly to splenocytes from syngeneic wild-type mice, no doubt reflecting the unique peptide complement carried by class II molecules in mutant animals. ..