Gene Symbol: Cd74
Description: CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)
Alias: CLIP, DHLAG, HLADG, Ia-GAMMA, H-2 class II histocompatibility antigen gamma chain, HLA-DR-GAMMA, Ia-associated invariant chain, MHC class II-associated invariant chain, class II-associated invariant chain peptide, dinucleotide microsatellite, histocompatibility: class II antigens, gamma chain of, ia antigen-associated invariant chain, invariant polypeptide of major histocompatibility complex, class II antigen-associated
Species: mouse
Products:     Cd74

Top Publications

  1. Barton G, Beers C, deRoos P, Eastman S, Gomez M, Forbush K, et al. Positive selection of self-MHC-reactive T cells by individual peptide-MHC class II complexes. Proc Natl Acad Sci U S A. 2002;99:6937-42 pubmed
    ..Our results suggest that individual peptide-MHC complexes positively select different subsets of self-MHC-reactive T cells and that the conformation of the peptide-MHC complex may contribute to this process. ..
  2. Elliott E, Drake J, Amigorena S, Elsemore J, Webster P, Mellman I, et al. The invariant chain is required for intracellular transport and function of major histocompatibility complex class II molecules. J Exp Med. 1994;179:681-94 pubmed
    ..Thus, although alpha and beta chains can fold and form dimers on their own, the absence of Ii chain causes them to be recognized as "misfolded" and retained in the same compartments as bona fide misfolded proteins. ..
  3. Wong P, Goldrath A, Rudensky A. Competition for specific intrathymic ligands limits positive selection in a TCR transgenic model of CD4+ T cell development. J Immunol. 2000;164:6252-9 pubmed
    ..To examine this, we analyzed positive selection in a transgenic mouse carrying a TCR specific for the human CLIP:I-Ab class II complex...
  4. Slavin A, Soos J, Stuve O, Patarroyo J, Weiner H, Fontana A, et al. Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. J Clin Invest. 2001;108:1133-9 pubmed
    ..Our results indicate that processing is required for initial Ag presentation and CNS T cell activation and suggest that autopathogenic peptides of CNS autoantigen may not be readily available for presentation without processing. ..
  5. Viville S, Neefjes J, Lotteau V, Dierich A, LeMeur M, Ploegh H, et al. Mice lacking the MHC class II-associated invariant chain. Cell. 1993;72:635-48 pubmed
    ..Consequently, mutant cells present protein antigens very poorly and mutant mice are deficient in producing and at negatively selecting CD4+ T cells. ..
  6. Bikoff E, Germain R, Robertson E. Allelic differences affecting invariant chain dependency of MHC class II subunit assembly. Immunity. 1995;2:301-10 pubmed
    ..The contribution of invariant chain to subunit assembly thus differs for allelic variants, suggesting that sequential associations of alpha, beta, and invariant chain may be affected by polymorphic differences. ..
  7. 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. ..
  8. 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. ..
  9. Beisner D, Langerak P, Parker A, Dahlberg C, Otero F, Sutton S, et al. The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain. J Exp Med. 2013;210:23-30 pubmed publisher
    ..Proteomic analysis identified the invariant chain (CD74) as a key substrate of Sppl2a and suggests that regulated intramembrane proteolysis of CD74 by Sppl2a contributes ..

More Information


  1. Boes M, van der Wel N, Peperzak V, Kim Y, Peters P, Ploegh H. In vivo control of endosomal architecture by class II-associated invariant chain and cathepsin S. Eur J Immunol. 2005;35:2552-62 pubmed
    ..Proper degradation of Ii is thus essential for normal endosomal morphology in antigen-presenting cells in vivo. ..
  2. Brown D, Swier K, Moskowitz N, Naujokas M, Locksley R, Reiner S. T helper subset differentiation in the absence of invariant chain. J Exp Med. 1997;185:31-41 pubmed
  3. Matza D, Lantner F, Bogoch Y, Flaishon L, Hershkoviz R, Shachar I. Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity. Proc Natl Acad Sci U S A. 2002;99:3018-23 pubmed
    ..We demonstrate in vivo that Ii N-terminal domain is directly involved in the maturation of B cells and is sufficient to promote B cell differentiation. ..
  4. Bodmer H, Viville S, Benoist C, Mathis D. Diversity of endogenous epitopes bound to MHC class II molecules limited by invariant chain. Science. 1994;263:1284-6 pubmed
    ..Thus, the influence of Ii on presentation does not follow simple rules. In addition, mice expressing Ii were not tolerant to epitopes unmasked in its absence, a finding with possible implications for autoimmunity. ..
  5. Barton G, Rudensky A. Requirement for diverse, low-abundance peptides in positive selection of T cells. Science. 1999;283:67-70 pubmed
    ..This requirement for peptide diversity indicates that the interaction between self peptides and T cell receptors during positive selection is highly specific. ..
  6. Topilski I, Harmelin A, Flavell R, Levo Y, Shachar I. Preferential Th1 immune response in invariant chain-deficient mice. J Immunol. 2002;168:1610-7 pubmed
    ..Therefore, we suggest that defective Ag presentation in Ii(-/-) mice leads selectively to a Th1 effector response. ..
  7. Grubin C, Kovats S, deRoos P, Rudensky A. Deficient positive selection of CD4 T cells in mice displaying altered repertoires of MHC class II-bound self-peptides. Immunity. 1997;7:197-208 pubmed
    ..In addition, the data suggest that T cell receptor repertoires selected in wild-type mice and in mice displaying limited spectra of self-peptides are distinct. ..
  8. Lantner F, Starlets D, Gore Y, Flaishon L, Yamit Hezi A, Dikstein R, et al. CD74 induces TAp63 expression leading to B-cell survival. Blood. 2007;110:4303-11 pubmed
    ..We recently demonstrated that cell surface CD74 controls mature B-cell survival...
  9. Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F, et al. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature. 2003;422:164-9 pubmed
    ..This indicates that MAIT cells are probably involved in the host response at the site of pathogen entry, and may regulate intestinal B-cell activity. ..
  10. Shi X, Leng L, Wang T, Wang W, Du X, Li J, et al. CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity. 2006;25:595-606 pubmed
    The macrophage migration inhibitory factor (MIF) receptor (CD74) was cloned recently, but the signaling mechanism is not evident...
  11. Takaesu N, Lower J, Robertson E, Bikoff E. Major histocompatibility class II peptide occupancy, antigen presentation, and CD4+ T cell function in mice lacking the p41 isoform of invariant chain. Immunity. 1995;3:385-96 pubmed
    ..In short, MHC class II expression and function are surprisingly unaffected in mice lacking p41 invariant chain, implying that the p31 and p41 isoforms may be functionally redundant in the intact animal. ..
  12. Kenty G, Martin W, van Kaer L, Bikoff E. MHC class II expression in double mutant mice lacking invariant chain and DM functions. J Immunol. 1998;160:606-14 pubmed
    ..These mutant mice lacking both Ii chain and DM activities should prove useful for analyzing nonconventional class II Ag presentation under normal physiological conditions in the intact animal...
  13. Schori H, Shechter R, Shachar I, Schwartz M. Genetic manipulation of CD74 in mouse strains of different backgrounds can result in opposite responses to central nervous system injury. J Immunol. 2007;178:163-71 pubmed
    The ability to recover from CNS injuries is strain dependent. Transgenic mice that weakly express the p41 CD74 isoform (an integral membrane protein functioning as a MHC class II chaperone) on an I-A(b) genetic background have normal CD4(+..
  14. Schneppenheim J, Dressel R, Hüttl S, Lüllmann Rauch R, Engelke M, Dittmann K, et al. The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain. J Exp Med. 2013;210:41-58 pubmed publisher
    ..We show that the invariant chain (li, CD74) of the major histocompatability class II complex (MHCII) undergoes intramembrane proteolysis mediated by SPPL2a...
  15. Starlets D, Gore Y, Binsky I, Haran M, Harpaz N, Shvidel L, et al. Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival. Blood. 2006;107:4807-16 pubmed
    b>CD74 is an integral membrane protein that was thought to function mainly as an MHC class II chaperone. However, CD74 was recently shown to have a role as an accessory-signaling molecule...
  16. Lennon Dumenil A, Roberts R, Valentijn K, Driessen C, Overkleeft H, Erickson A, et al. The p41 isoform of invariant chain is a chaperone for cathepsin L. EMBO J. 2001;20:4055-64 pubmed
    ..This suggests that p41 is not merely an inhibitor of CatL enzymatic activity, but serves as a chaperone to help maintain a pool of mature enzyme in late-endocytic compartments of antigen-presenting cells. ..
  17. Shachar I, Elliott E, Chasnoff B, Grewal I, Flavell R. Reconstitution of invariant chain function in transgenic mice in vivo by individual p31 and p41 isoforms. Immunity. 1995;3:373-83 pubmed
    ..Furthermore, p31 and p41 retrieve the CD4+ T cell population, which is reduced in the (delta Ii) mice. Moreover, the immune response to protein antigen is restored by both isoforms. ..
  18. Wong P, Rudensky A. Phenotype and function of CD4+ T cells in mice lacking invariant chain. J Immunol. 1996;156:2133-42 pubmed
    ..These results suggest that the altered thymic peptide repertoire displayed by class II molecules in the absence of Ii has a dramatic impact on the selection of CD4+ T cells and their phenotype in the periphery. ..
  19. Battegay M, Bachmann M, Burhkart C, Viville S, Benoist C, Mathis D, et al. Antiviral immune responses of mice lacking MHC class II or its associated invariant chain. Cell Immunol. 1996;167:115-21 pubmed
    ..This suggests that local protein concentrations reached during viral infection in the host are high enough to override the Ii deficiency of antigen-presenting cells in vivo. ..
  20. Leng L, Metz C, Fang Y, Xu J, Donnelly S, Baugh J, et al. MIF signal transduction initiated by binding to CD74. J Exp Med. 2003;197:1467-76 pubmed
    ..Using expression cloning and functional analysis, we report herein that CD74, a Type II transmembrane protein, is a high-affinity binding protein for MIF...
  21. Bikoff E, Kenty G, van Kaer L. Distinct peptide loading pathways for MHC class II molecules associated with alternative Ii chain isoforms. J Immunol. 1998;160:3101-10 pubmed
    ..mice expressing either Ii chain isoform appear equally occupied by class II-associated Ii chain-derived peptides (CLIP). Surprisingly, in functional assays, these novel mouse strains exhibit strikingly different phenotypes...
  22. Benlagha K, Park S, Guinamard R, Forestier C, Karlsson L, Chang C, et al. Mechanisms governing B cell developmental defects in invariant chain-deficient mice. J Immunol. 2004;172:2076-83 pubmed
    ..These findings reveal unexpected consequences of Ii deficiency on the development and organization of B cell follicles. ..
  23. Tourne S, Miyazaki T, Wolf P, Ploegh H, Benoist C, Mathis D. Functionality of major histocompatibility complex class II molecules in mice doubly deficient for invariant chain and H-2M complexes. Proc Natl Acad Sci U S A. 1997;94:9255-60 pubmed
    ..complexes may almost all derive from invariant chain and (ii) that H-2M complexes edit the peptide array displayed on thymic stromal cells in the absence of invariant chain, showing that it can edit, in vivo, peptides other than CLIP.
  24. Shachar I, Flavell R. Requirement for invariant chain in B cell maturation and function. Science. 1996;274:106-8 pubmed
    ..This block was independent of major histocompatability complex class II expression and was an intrinsic feature of B cells that correlated with the amount of Ii. Thus, Ii participates by an unknown mechanism in B cell maturation. ..
  25. Karlsson L, Peleraux A, Lindstedt R, Liljedahl M, Peterson P. Reconstitution of an operational MHC class II compartment in nonantigen-presenting cells. Science. 1994;266:1569-73 pubmed
    ..The data presented show that H-2M, class II, and li are the minimally required components for efficient formation of stable class II-peptide complexes, and thus for a functional class II compartment. ..
  26. Koch N, Lauer W, Habicht J, Dobberstein B. Primary structure of the gene for the murine Ia antigen-associated invariant chains (Ii). An alternatively spliced exon encodes a cysteine-rich domain highly homologous to a repetitive sequence of thyroglobulin. EMBO J. 1987;6:1677-83 pubmed
  27. Gore Y, Starlets D, Maharshak N, Becker Herman S, Kaneyuki U, Leng L, et al. Macrophage migration inhibitory factor induces B cell survival by activation of a CD74-CD44 receptor complex. J Biol Chem. 2008;283:2784-92 pubmed
    ..It was previously shown that in macrophages, MIF binds to a complex of CD74 and CD44, resulting in initiation of a signaling pathway...
  28. Kenty G, Bikoff E. BALB/c invariant chain mutant mice display relatively efficient maturation of CD4+ T cells in the periphery and secondary proliferative responses elicited upon peptide challenge. J Immunol. 1999;163:232-41 pubmed
    ..The milder phenotype displayed by BALB/c Ii chain mutants in comparison with class II functional defects previously described for mouse strains lacking Ii chain is likely to have an effect on disease susceptibility. ..
  29. Takaesu N, Lower J, Yelon D, Robertson E, Bikoff E. In vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain. J Immunol. 1997;158:187-99 pubmed
  30. Bikoff E, Huang L, Episkopou V, van Meerwijk J, Germain R, Robertson E. Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression. J Exp Med. 1993;177:1699-712 pubmed
    ..Overall, this striking phenotype establishes that the invariant chain plays a critical role in regulating MHC class II expression and function in the intact animal. ..
  31. Faure André G, Vargas P, Yuseff M, Heuzé M, Diaz J, Lankar D, et al. Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain. Science. 2008;322:1705-10 pubmed publisher
    ..We found that the major histocompatibility complex II-associated invariant chain (Ii or CD74), a known regulator of antigen processing, negatively regulates DC motility in vivo...
  32. Eades A, Litfin M, Rahmsdorf H. The IFN-gamma response of the murine invariant chain gene is mediated by a complex enhancer that includes several MHC class II consensus elements. J Immunol. 1990;144:4399-409 pubmed
    ..A protein binding to the central part of the IFN-gamma response element was detectable in gel retardation experiments; it was active only in extracts from IFN-gamma-treated cells. ..
  33. Bergmann H, Yabas M, Short A, Miosge L, Barthel N, Teh C, et al. B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8- dendritic cells require the intramembrane endopeptidase SPPL2A. J Exp Med. 2013;210:31-40 pubmed publisher
    ..CD8-negative dendritic cells were also greatly decreased. SPPL2A deficiency blocked the proteolytic processing of CD74 MHC II invariant chain in both cell types, causing dramatic build-up of the p8 product of Cathepsin S and ..
  34. 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. ..
  35. Maehr R, Kraus M, Ploegh H. Mice deficient in invariant-chain and MHC class II exhibit a normal mature B2 cell compartment. Eur J Immunol. 2004;34:2230-6 pubmed
    ..We suggest that neither Ii itself, nor the MHC class II products are required for normal B cell development. ..
  36. Wang J, Tong C, Yan X, Yeung E, Gandavadi S, Hare A, et al. Limiting cardiac ischemic injury by pharmacological augmentation of macrophage migration inhibitory factor-AMP-activated protein kinase signal transduction. Circulation. 2013;128:225-36 pubmed publisher
    ..These data support the pharmacological utility of small-molecule MIF agonists in enhancing AMPK activation and reducing cardiac ischemic injury. ..
  37. Hsieh C, Chen C, Lin Y, Yeh T, Tsai T, Hong M, et al. Macrophage migration inhibitory factor triggers chemotaxis of CD74+CXCR2+ NKT cells in chemically induced IFN-γ-mediated skin inflammation. J Immunol. 2014;193:3693-703 pubmed publisher
    ..MIF specifically triggered the chemotaxis of NKT cells via CD74 and CXCR2, and the resulting depletion of NKT cells abolished TPA-induced skin inflammation...
  38. Sauler M, Zhang Y, Min J, Leng L, Shan P, Roberts S, et al. Endothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury. FASEB J. 2015;29:1940-9 pubmed publisher
    ..We postulate that the MIF receptor CD74 mediates this protective effect...
  39. Fan L, Busser B, Lifsted T, Oukka M, Lo D, Laufer T. Antigen presentation by keratinocytes directs autoimmune skin disease. Proc Natl Acad Sci U S A. 2003;100:3386-91 pubmed
    ..Disease can be induced by skin inflammation but not solely by activation of T cells. Thus, cutaneous immunopathology can be directed through antigen presentation by tissue-resident keratinocytes to autoreactive TCR Tg CD4(+) cells. ..
  40. Bank L, Bianchi L, Ebisu F, Lerman Sinkoff D, Smiley E, Shen Y, et al. Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear. Development. 2012;139:4666-74 pubmed publisher
    ..A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons...
  41. Salek Ardakani S, Flynn R, Arens R, Yagita H, Smith G, Borst J, et al. The TNFR family members OX40 and CD27 link viral virulence to protective T cell vaccines in mice. J Clin Invest. 2011;121:296-307 pubmed publisher
    ..Our results suggest that the virulence of a virus dictates costimulatory receptor usage to determine the level of protective CD8+ T cell immunity. ..
  42. Rinderknecht C, Lu N, Crespo O, Truong P, Hou T, Wang N, et al. I-Ag7 is subject to post-translational chaperoning by CLIP. Int Immunol. 2010;22:705-16 pubmed publisher
    ..with autoimmune diseases form unusually low-stability complexes with class II-associated invariant chain peptides (CLIP), leading us to hypothesize that this is an important feature contributing to autoimmune pathogenesis...
  43. Shi G, Bryant R, Riese R, Verhelst S, Driessen C, Li Z, et al. Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. J Exp Med. 2000;191:1177-86 pubmed
    ..Such loading occurs after endosomal degradation of the invariant chain to a approximately 3-kD peptide termed CLIP (class II-associated invariant chain peptide)...
  44. Rickard S, Ono S. Invariant chain+ N2a neuroblastoma cells stably expressing the class II MHC transactivator CIITA fail to stimulate anti-tumor immunity. Exp Mol Pathol. 2008;85:147-54 pubmed publisher
    ..This absence of an anti-tumor immune response despite MHC II expression is likely due to the presence of invariant chain, in support of the MHCII(+)/Ii(-) paradigm. ..
  45. Terauchi M, Li J, Bedi B, Baek K, Tawfeek H, Galley S, et al. T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling. Cell Metab. 2009;10:229-40 pubmed publisher
  46. Pierre P, Shachar I, Matza D, Gatti E, Flavell R, Mellman I. Invariant chain controls H2-M proteolysis in mouse splenocytes and dendritic cells. J Exp Med. 2000;191:1057-62 pubmed
    ..Thus, Ii chain may act as a lysosomal protease inhibitor in B cells and DCs, with its deletion contributing indirectly to the loss of H2-M. ..
  47. Vandenbark A, Meza Romero R, Benedek G, Andrew S, Huan J, Chou Y, et al. A novel regulatory pathway for autoimmune disease: binding of partial MHC class II constructs to monocytes reduces CD74 expression and induces both specific and bystander T-cell tolerance. J Autoimmun. 2013;40:96-110 pubmed publisher
    ..involves RTL binding to CD11b(+) mononuclear cells through a receptor comprised of MHC class II invariant chain (CD74), cell-surface histones and MHC class II itself for treatment of experimental autoimmune encephalomyelitis (EAE)...
  48. Liu Y, Teige A, Mondoc E, Ibrahim S, Holmdahl R, Issazadeh Navikas S. Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice. J Clin Invest. 2011;121:249-64 pubmed publisher
    ..Given the results, endogenous collagen peptide activators of NKT cells may offer promise as novel therapeutics in tissue-specific autoimmune and inflammatory diseases...
  49. Neumann J, König A, Koch N. Detection of aberrant association of DM with MHC class II subunits in the absence of invariant chain. Int Immunol. 2007;19:31-9 pubmed
    ..These non-classical MHC class II molecules catalyze the release of the invariant chain (Ii) fragment CLIP from the class II cleft and facilitate acquisition of antigenic peptides by MHC class II peptide receptors...
  50. Sevilla L, Comstock S, Swier K, Miller J. Endoplasmic reticulum-associated degradation-induced dissociation of class II invariant chain complexes containing a glycosylation-deficient form of p41. J Immunol. 2004;173:2586-93 pubmed
    ..These results suggest that the ERAD machinery can induce subunit disassembly, specifically targeting misfolded subunits to degradation and sparing properly folded subunits for reassembly and/or export. ..
  51. Flaishon L, Hershkoviz R, Lantner F, Lider O, Alon R, Levo Y, et al. Autocrine secretion of interferon gamma negatively regulates homing of immature B cells. J Exp Med. 2000;192:1381-8 pubmed
    ..Perturbation of interferon gamma activity in vivo leads to the homing of immature B cells to the lymph nodes. This is the first example of autocrine regulation of immune cell migration to sites of foreign antigen presentation. ..
  52. Voutsas I, Gritzapis A, Mahaira L, Salagianni M, Von Hofe E, Kallinteris N, et al. Induction of potent CD4+ T cell-mediated antitumor responses by a helper HER-2/neu peptide linked to the Ii-Key moiety of the invariant chain. Int J Cancer. 2007;121:2031-41 pubmed
    ..Our data show that Ii-Key modified HER-2/neu776-790 hybrid peptides are sufficiently potent to provide antigen-specific CD4+ TH cells with therapeutic antitumor activity. ..
  53. Ness T, Ewing J, Hogaboam C, Kunkel S. CCR4 is a key modulator of innate immune responses. J Immunol. 2006;177:7531-9 pubmed
    ..These data stress the importance of CCR4 in macrophage differentiation and innate immune responses to pathogens, as well as the involvement of chemokine receptor expression in TLR signaling regulation. ..
  54. Kamala T, Nanda N. Protective response to Leishmania major in BALB/c mice requires antigen processing in the absence of DM. J Immunol. 2009;182:4882-90 pubmed publisher
    ..major infections. This report suggests a novel mechanism to trigger host resistance against pathogens. ..
  55. Klasen C, Ohl K, Sternkopf M, Shachar I, Schmitz C, Heussen N, et al. MIF promotes B cell chemotaxis through the receptors CXCR4 and CD74 and ZAP-70 signaling. J Immunol. 2014;192:5273-84 pubmed publisher
    ..Splenic B cells express CXCR4 and the receptor CD74 but not CXCR2...
  56. Barton G, Rudensky A. An altered invariant chain protein with an antigenic peptide in place of CLIP forms SDS-stable complexes with class II alphabeta dimers and facilitates highly efficient peptide loading. Int Immunol. 1998;10:1159-65 pubmed
    ..We have constructed a cassette which allows for the replacement of the CLIP region of invariant chain (Ii) with an antigenic peptide...
  57. Genève L, Ménard C, Labrecque N, Thibodeau J. The p35 human invariant chain in transgenic mice restores mature B cells in the absence of endogenous CD74. Int Immunol. 2012;24:645-60 pubmed
    The invariant chain (Ii; CD74) has pleiotropic functions and Ii-deficient mice show defects in MHC class II (MHC II) transport and B cell maturation...
  58. Zielinski C, Jacob S, Bouzahzah F, Ehrlich B, Craft J. Naive CD4+ T cells from lupus-prone Fas-intact MRL mice display TCR-mediated hyperproliferation due to intrinsic threshold defects in activation. J Immunol. 2005;174:5100-9 pubmed
    ..This genetically altered threshold for activation of MRL T cells, a consequence of a proximal defect in CD3-mediated signal transduction, may contribute to the abrogation of T cell tolerance to self-Ags in lupus. ..
  59. Kolk D, Floyd Smith G. The HXY box regulatory element modulates expression of the murine IA antigen-associated invariant chain in L fibroblasts. DNA Cell Biol. 1992;11:745-54 pubmed
  60. Chatterjee P, Chiasson V, Seerangan G, De Guzman E, Milad M, Bounds K, et al. Depletion of MHC class II invariant chain peptide or ?-? T-cells ameliorates experimental preeclampsia. Clin Sci (Lond). 2017;131:2047-2058 pubmed publisher
    ..receptor (TLR) activation induces major histocompatibility complex (MHC) class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause PE-like features in mice...
  61. Maharshak N, Cohen S, Lantner F, Hart G, Leng L, Bucala R, et al. CD74 is a survival receptor on colon epithelial cells. World J Gastroenterol. 2010;16:3258-66 pubmed
    To investigate the expression and function of CD74 in normal murine colon epithelial cells (CEC) and colon carcinoma cells.
  62. Koonce C, Wutz G, Robertson E, Vogt A, Kropshofer H, Bikoff E. DM loss in k haplotype mice reveals isotype-specific chaperone requirements. J Immunol. 2003;170:3751-61 pubmed
    ..DM mutant cells studied to date express class II bound by class II-associated invariant chain-derived peptide (CLIP), a short proteolytic fragment of the invariant chain, and exhibit defective peptide-loading abilities...
  63. Golovkina T, Agafonova Y, Kazansky D, Chervonsky A. Diverse repertoire of the MHC class II-peptide complexes is required for presentation of viral superantigens. J Immunol. 2001;166:2244-50 pubmed
    ..Thus, MHC class II peptide repertoire is critical for recognition of v-Sag by the T cells and affects the outcome of infection with a retrovirus. ..
  64. Honey K, Forbush K, Jensen P, Rudensky A. Effect of decreasing the affinity of the class II-associated invariant chain peptide on the MHC class II peptide repertoire in the presence or absence of H-2M. J Immunol. 2004;172:4142-50 pubmed
    The class II-associated invariant chain peptide (CLIP) region of the invariant chain (Ii) directly influences MHC class II presentation by occupying the MHC class II peptide-binding groove, thereby preventing premature loading of peptides...
  65. Ghoochani A, Schwarz M, Yakubov E, Engelhorn T, Doerfler A, Buchfelder M, et al. MIF-CD74 signaling impedes microglial M1 polarization and facilitates brain tumorigenesis. Oncogene. 2016;35:6246-6261 pubmed publisher
    ..We show that brain tumors escape pro-inflammatory M1 conversion of microglia via CD74 activation through the secretion of the cytokine macrophage migration inhibitory factor (MIF), which results in a ..
  66. Meza Romero R, Benedek G, Yu X, Mooney J, Dahan R, Duvshani N, et al. HLA-DR?1 constructs block CD74 expression and MIF effects in experimental autoimmune encephalomyelitis. J Immunol. 2014;192:4164-73 pubmed publisher
    b>CD74, the cell-surface form of the MHC class II invariant chain, is a key inflammatory factor that is involved in various immune-mediated diseases as part of the macrophage migration inhibitory factor (MIF) binding complex...
  67. Martin H, Santoro M, Mustafa S, Riedel G, Forrester J, Teismann P. Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease. Glia. 2016;64:386-95 pubmed publisher
    ..These data indicate that in addition to microglial cell/myeloid cell activation MHC Class II-mediated T cell activation is required for the full expression of pathology in this model of PD. ..
  68. D Amato Brito C, Cipriano D, Colin D, Germain S, Seimbille Y, Robert J, et al. Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma. Oncotarget. 2016;7:11512-25 pubmed publisher
    ..Our group recently identified the MIF-receptor CD74 as an independent prognostic factor for overall survival in patients with malignant pleural mesothelioma...