Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cutting edge: FcR-like 6 is an MHC class II receptor.

ABSTRACT: Receptors for the Fc portion of Ig have been extensively characterized and are known to regulate humoral responses, but members of the closely related FcR-like (FCRL) family have not been found to bind Ig, and to date, no ligand has been identified for any FCRL. Using a cell-based GFP reporter system and a recombinant Fc chimeric protein, we show that human FCRL6, a receptor selectively expressed by cytotoxic T and NK cells, directly binds HLA-DR, an MHC class II molecule. Given the similarity among constant regions of Ig and MHC molecules, these findings suggest that representatives of the FcR and FCRL multigene families may have independently evolved to engage two ancestral elements fundamental to adaptive immunity. This discovery may offer new insight into the interaction between cytotoxic lymphocytes and APCs and may have important implications for better understanding HLA disease susceptibility and pathogenesis.

SUBMITTER: Schreeder DM

PROVIDER: S-EPMC4876727 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Cutting edge: FcR-like 6 is an MHC class II receptor.

Schreeder Daniel M DM Cannon John P JP Wu Jiongru J Li Ran R Shakhmatov Mikhail A MA Davis Randall S RS

Journal of immunology (Baltimore, Md. : 1950) 20100602 1

Receptors for the Fc portion of Ig have been extensively characterized and are known to regulate humoral responses, but members of the closely related FcR-like (FCRL) family have not been found to bind Ig, and to date, no ligand has been identified for any FCRL. Using a cell-based GFP reporter system and a recombinant Fc chimeric protein, we show that human FCRL6, a receptor selectively expressed by cytotoxic T and NK cells, directly binds HLA-DR, an MHC class II molecule. Given the similarity a ...[more]

PMID: 20519654

Similar Datasets

Cutting edge: FcR-like 5 on innate B cells is targeted by a poxvirus MHC class I-like immunoevasin.

Project description:Under selective pressure from host immunity, viruses have retained genes encoding immunoevasins, molecules interfering with host viral recognition and clearance. Due to their binding specificities, immunoevasins can be exploited as affinity labels to identify host-encoded molecules of previously unsuspected importance in defense against the relevant class of virus. We previously described an orthopoxvirus MHC class I-like protein (OMCP) that binds with high affinity to the activating receptor NKG2D on NK and T cell subsets, implicating NKG2D in antiorthopoxvirus immunity. In this study, we report that OMCP also binds in an NKG2D-independent manner to B cells and monocytes/macrophages. We identify murine FcR-like 5 (FCRL5), an orphan immunoregulatory protein highly expressed by innate B lymphocytes, as a specific receptor for OMCP. The three N-terminal Ig domains of FCRL5 are required for OMCP binding. The targeting of FCRL5 by an orthopoxvirus immunoevasin strongly implicates it in contributing to host defense against zoonotic orthopoxviruses.

| S-EPMC3321838 | biostudies-literature

Cutting edge: NADPH oxidase modulates MHC class II antigen presentation by B cells.

Project description:Phagocyte NADPH oxidase plays a key role in pathogen clearance via reactive oxygen species (ROS) production. Defects in oxidase function result in chronic granulomatous disease with hallmark recurrent microbial infections and inflammation. The oxidase's role in the adaptive immune response is not well understood. Class II presentation of cytoplasmic and exogenous Ag to CD4(+) T cells was impaired in human B cells with reduced oxidase p40(phox) subunit expression. Naturally arising mutations, which compromise p40(phox) function in a chronic granulomatous disease patient, also perturbed class II Ag presentation and intracellular ROS production. Reconstitution of patient B cells with a wild-type, but not a mutant, p40(phox) allele restored exogenous Ag presentation and intracellular ROS generation. Remarkably, class II presentation of epitopes from membrane Ag was robust in p40(phox)-deficient B cells. These studies reveal a role for NADPH oxidase and p40(phox) in skewing epitope selection and T cell recognition of self Ag.

| S-EPMC3466399 | biostudies-literature

Cutting Edge: Selective role of ubiquitin in MHC class I antigen presentation.

Project description:The importance of ubiquitination in MHC class I-restricted Ag processing remains unclear. To address this issue, we overexpressed wild-type and dominant-negative lysineless forms of ubiquitin (Ub) in mammalian cells using an inducible vaccinia virus system. Overexpression of the lysineless Ub nearly abrogated polyubiquitination and potently inhibited epitope presentation from a cytosolic N-end rule substrate as well as endoplasmic reticulum (ER)-targeted model Ags. In contrast, there was little impact on Ag presentation from cytosolic proteins. These trends were location dependent; redirecting cytosolic Ag to the ER rendered presentation lysineless Ub-sensitive, whereas retargeting exocytic Ag to the cytosol had the inverse effect. This dichotomy was further underscored by small interfering RNA knockdown of the ER-associated Ub ligase Hrd1. Thus, Ub-dependent degradation appears to play a major role in the MHC class I-restricted processing of ER-targeted proteins and a more restricted role in the processing of cytosolic proteins.

| S-EPMC3650468 | biostudies-literature

Cutting edge: impaired MHC class I expression in mice deficient for Nlrc5/class I transactivator.

Project description:MHC class I and class II are crucial for the adaptive immune system. Although regulation of MHC class II expression by CIITA has long been recognized, the mechanism of MHC class I transactivation has been largely unknown until the recent discovery of NLRC5/class I transactivator. In this study, we show using Nlrc5-deficient mice that NLRC5 is required for both constitutive and inducible MHC class I expression. Loss of Nlrc5 resulted in severe reduction in the expression of MHC class I and related genes such as ?(2)-microglobulin, Tap1, or Lmp2, but did not affect MHC class II levels. IFN-? stimulation could not overcome the impaired MHC class I expression in Nlrc5-deficient cells. Upon infection with Listeria monocyogenes, Nlrc5-deficient mice displayed impaired CD8(+) T cell activation, accompanied with increased bacterial loads. These findings illustrate critical roles of NLRC5/class I transactivator in MHC class I gene regulation and host defense by CD8(+) T cell responses.

| S-EPMC3578426 | biostudies-literature

Cutting edge: MHC class II expression by pulmonary nonhematopoietic cells plays a critical role in controlling local inflammatory responses.

Project description:The interaction of CD4(+) T cells with MHC class II (MHCII)-expressing hematopoietic APCs plays a critical role in both the generation of protective immune responses and maintenance of tolerance in the lung. The functional significance of MHCII expression by nonhematopoietic stromal cells, however, has not been defined in vivo. Using a novel mouse model of orthotopic left lung transplantation, we demonstrate that selective elimination of MHCII expression on nonhematopoietic cells leads to an inflammatory response as a result of reduced peripheral generation of regulatory CD4(+) T cells. Absence of MHCII expression on nonhematopoietic cells also inhibits local growth of metastatic pulmonary tumor. These findings indicate that nonhematopoietic cells play a previously unrecognized role in downregulating inflammatory responses in nonlymphoid tissues.

| S-EPMC3897247 | biostudies-literature

Cutting edge: permissive MHC class II allele changes the pattern of antitumor immune response resulting in failure of tumor rejection.

Project description:We studied the growth of transgenic adenocarcinoma of mouse prostate (TRAMP)-C1 tumor cells expressing human prostate-specific Ag (PSA) in HLA-DRB1*1501 (DR2b) transgenic mice. TRAMP-PSA tumors were frequently rejected by HLA-DR2b(-) mice but had increased incidence in HLA-DR2b(+) littermates. The levels of PSA-specific CD8 T cell responses were significantly higher in the HLA-DR2b(-) mice that rejected TRAMP-PSA tumors compared with HLA-DR2b(+) tumor-bearing littermates. In contrast, Ab responses to PSA were strong in HLA-DR2b(+) mice bearing TRAMP-PSA tumors and were virtually undetectable in HLA-DR2b(-) littermates. The analysis of CD4 T cell responses to PSA revealed the presence of several CD4 T cell epitopes in HLA-DR2b(+) mice but failed to identify strong I-A(b)-restricted epitopes in HLA-DR2b(-) mice. Our data demonstrate that the expression of a permissive HLA class II allele can change the pattern of the immune response to a tumor Ag, resulting in the failure of tumor rejection.

| S-EPMC2743899 | biostudies-literature

Cutting edge: antibody-dependent memory-like NK cells distinguished by FcR? deficiency.

Project description:Because NK cells lack gene-recombination machinery and are thought to be relatively short-lived, it is unclear whether NK cells can mount long-term effective recall responses to reinfections by diverse pathogens. In this article, we report that FcR?-deficient NK cells, which we recently identified and termed g(-)NK cells, possess distinct memory features directed by FcR-mediated Ab-dependent target recognition. The presence of g(-)NK cells was associated with prior human CMV (HMCV) infection, yet g(-)NK cell responses were not restricted to HCMV-infected target cells. In the presence of virus-specific Abs, g(-)NK cells had greatly enhanced functional capabilities, superior to conventional NK cells, and were highly responsive to cells infected with either HCMV or HSV-1. Remarkably, the g(-)NK cell subset persisted long-term at nearly constant levels in healthy individuals. Therefore, FcR? deficiency distinguishes an Ab-dependent memory-like NK cell subset with enhanced potential for broad antiviral responses.

| S-EPMC3623944 | biostudies-literature

Cutting edge: HLA-DM functions through a mechanism that does not require specific conserved hydrogen bonds in class II MHC-peptide complexes.

Project description:HLA-DM catalyzes peptide dissociation and exchange in class II MHC molecules through a mechanism that has been proposed to involve the disruption of specific components of the conserved hydrogen bond network in MHC-peptide complexes. HLA-DR1 molecules with alanine substitutions at each of the six conserved H- bonding positions were expressed in cells, and susceptibility to DM catalytic activity was evaluated by measuring the release of CLIP. The mutants alphaN62A, alphaN69A, alphaR76A, and betaH81A DR1 were fully susceptible to DM-mediated CLIP release, and betaN82A resulted in spontaneous release of CLIP. Using recombinant soluble DR1 molecules, the amino acid betaN82 was observed to contribute disproportionately in stabilizing peptide complexes. Remarkably, the catalytic potency of DM with each beta-chain mutant was equal to or greater than that observed with wild-type DR1. Our results support the conclusion that no individual component of the conserved hydrogen bond network plays an essential role in the DM catalytic mechanism.

| S-EPMC2912111 | biostudies-literature

Cutting edge: Conditional MHC class II expression reveals a limited role for B cell antigen presentation in primary and secondary CD4 T cell responses.

Project description:The activation, differentiation, and subsequent effector functions of CD4 T cells depend on interactions with a multitude of MHC class II (MHCII)-expressing APCs. To evaluate the individual contribution of various APCs to CD4 T cell function, we have designed a new murine tool for selective in vivo expression of MHCII in subsets of APCs. Conditional expression of MHCII in B cells was achieved using a cre-loxP approach. After i.v. or s.c. priming, partial proliferation and activation of CD4 T cells was observed in mice expressing MHCII only by B cells. Restricting MHCII expression to B cells constrained secondary CD4 T cell responses in vivo, as demonstrated in a CD4 T cell-dependent model of autoimmunity, experimental autoimmune encephalomyelitis. These results highlight the limitations of B cell Ag presentation during initiation and propagation of CD4 T cell function in vivo using a novel system to study individual APCs by the conditional expression of MHCII.

| S-EPMC3711531 | biostudies-literature

Cutting Edge: Inhibition of the Interaction of NK Inhibitory Receptors with MHC Class I Augments Antiviral and Antitumor Immunity.

Project description:NK cells recognize MHC class I (MHC-I) Ags via stochastically expressed MHC-I-specific inhibitory receptors that prevent NK cell activation via cytoplasmic ITIM. We have identified a pan anti-MHC-I mAb that blocks NK cell inhibitory receptor binding at a site distinct from the TCR binding site. Treatment of unmanipulated mice with this mAb disrupted immune homeostasis, markedly activated NK and memory phenotype T cells, enhanced immune responses against transplanted tumors, and augmented responses to acute and chronic viral infection. mAbs of this type represent novel checkpoint inhibitors in tumor immunity, potent tools for the eradication of chronic infection, and may function as adjuvants for the augmentation of the immune response to weak vaccines.

| S-EPMC7369225 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data