scholarly journals Activated human T lymphocytes express MHC class I heavy chains not associated with beta 2-microglobulin.

1990 ◽  
Vol 171 (5) ◽  
pp. 1431-1442 ◽  
Author(s):  
E Schnabl ◽  
H Stockinger ◽  
O Majdic ◽  
H Gaugitsch ◽  
I J Lindley ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Mhc Class I ◽  
Hla Class I ◽  
Class I ◽  
Heavy Chains ◽  
Human T Lymphocytes ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Mhc Class I Molecules

We present here the molecular characterization of a new activation-induced surface structure on human T lymphocytes, termed LA45, with high homology (93% at protein level) to MHC class I molecules. Antigen modulation and sequential immunoprecipitation experiments revealed that LA45 and HLA class I proteins do not crossreact with the corresponding antibodies. Furthermore, LA45 is not associated with beta 2-m. On the other hand, we could show that the separation of HLA-A,B,C and beta 2m molecules, induced by SDS-denaturation, leads to a conformational change in the heavy chain in such a way that it becomes reactive with LA45. The 90/45 kD LA45 proteins thus appear to be non-beta 2m-associated MHC class I alpha chains that are selectively expressed by activated but not by resting human T lymphocytes.

scholarly journals Translocation of peptides through microsomal membranes is a rapid process and promotes assembly of HLA-B27 heavy chain and beta 2-microglobulin translated in vitro.

1991 ◽  
Vol 115 (4) ◽  
pp. 959-970 ◽  
Author(s):  
F Lévy ◽  
R Larsson ◽  
S Kvist
Keyword(s):  
Mhc Class I ◽  
Heavy Chain ◽  
Peptide Binding ◽  
Class I ◽  
Hla B27 ◽  
Heavy Chains ◽  
Microsomal Membranes ◽  
Beta 2 ◽  
Beta 2 Microglobulin

We have translated major histocompatibility complex (MHC) class I heavy chains and human beta 2-microglobulin in vitro in the presence of microsomal membranes and a peptide from the nucleoprotein of influenza A. This peptide stimulates assembly of HLA-B27 heavy chain and beta 2-microglobulin about fivefold. By modifying this peptide to contain biotin at its amino terminus, we could precipitate HLA-B27 heavy chains with immobilized streptavidin, thereby directly demonstrating class I heavy chain-peptide association under close to physiological conditions. The biotin-modified peptide stimulates assembly to the same extent as the unmodified peptide. Both peptides bind to the same site on the HLA-B27 molecule. Immediately after synthesis of the HLA-B27 heavy chain has been completed, it assembles with beta 2-microglobulin and peptide. These interactions occur in the lumen of the microsomes (endoplasmic reticulum), demonstrating that the peptide must cross the microsomal membrane in order to promote assembly. The transfer of peptide across the microsomal membrane is a rapid process, as peptide binding to heavy chain-beta 2-microglobulin complexes is observed in less than 1 min after addition of peptide. By using microsomes deficient of beta 2-microglobulin (from Daudi cells), we find a strict requirement of beta 2-microglobulin for detection of peptide interaction with the MHC class I heavy chain. Furthermore, we show that heavy chain interaction with beta 2-microglobulin is likely to precede peptide binding. Biotin-modified peptides are likely to become a valuable tool in studying MHC antigen interaction and assembly.

Altered structure of HLA class I heavy chains associated with mouse beta-2 microglobulin

1985 ◽  
Vol 21 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Pierre Ferrie ◽  
Juan C. Fontecilla-Camps ◽  
Danielle Bucchini ◽  
Dani�le H. Caillol ◽  
Bertrand R. Jordan ◽  
...  
Keyword(s):  
Hla Class I ◽  
Class I ◽  
Heavy Chains ◽  
Beta 2 ◽  
Beta 2 Microglobulin

scholarly journals Identification and Molecular Characterization of Z/ZE Lineage MHC Class I Heavy Chain Homologue and ^|^beta;2-microglobulin from Rock Bream Oplegnathus fasciatus

2014 ◽  
Vol 49 (3) ◽  
pp. 93-112 ◽  
Author(s):  
Chamilani Nikapitiya ◽  
Sung-Ju Jung ◽  
Myung-Hwa Jung ◽  
Jun-Young Song ◽  
Jehee Lee ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Mhc Class I ◽  
Heavy Chain ◽  
Class I ◽  
Oplegnathus Fasciatus ◽  
Rock Bream ◽  
Beta 2 ◽  
Beta 2 Microglobulin

scholarly journals ERAP1 Controls the Interaction of the Inhibitory Receptor KIR3DL1 With HLA-B51:01 by Affecting Natural Killer Cell Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Silvia D’Amico ◽  
Valerio D’Alicandro ◽  
Mirco Compagnone ◽  
Patrizia Tempora ◽  
Giusy Guida ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Subset ◽  
Human Tumor ◽  
Hla Class I ◽  
Class I ◽  
Pharmacological Inhibition ◽  
Mhc Class I Molecules

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses by trimming peptides for presentation by major histocompatibility complex (MHC) class I molecules. Previously, we have shown that genetic or pharmacological inhibition of ERAP1 on murine and human tumor cell lines perturbs the engagement of NK cell inhibitory receptors Ly49C/I and Killer-cell Immunoglobulin-like receptors (KIRs), respectively, by their specific ligands (MHC class I molecules), thus leading to NK cell killing. However, the effect of ERAP1 inhibition in tumor cells was highly variable, suggesting that its efficacy may depend on several factors, including MHC class I typing. To identify MHC class I alleles and KIRs that are more sensitive to ERAP1 depletion, we stably silenced ERAP1 expression in human HLA class I-negative B lymphoblastoid cell line 721.221 (referred to as 221) transfected with a panel of KIR ligands (i.e. HLA-B*51:01, -Cw3, -Cw4 and -Cw7), or HLA-A2 which does not bind any KIR, and tested their ability to induce NK cell degranulation and cytotoxicity. No change in HLA class I surface expression was detected in all 221 transfectant cells after ERAP1 depletion. In contrast, CD107a expression levels were significantly increased on NK cells stimulated with 221-B*51:01 cells lacking ERAP1, particularly in the KIR3DL1-positive NK cell subset. Consistently, genetic or pharmacological inhibition of ERAP1 impaired the recognition of HLA-B*51:01 by the YTS NK cell overexpressing KIR3DL1*001, suggesting that ERAP1 inhibition renders HLA-B*51:01 molecules less eligible for binding to KIR3DL1. Overall, these results identify HLA-B*51:01/KIR3DL1 as one of the most susceptible combinations for ERAP1 inhibition, suggesting that individuals carrying HLA-B*51:01-like antigens may be candidates for immunotherapy based on pharmacological inhibition of ERAP1.

hDectin-1 Mediates Cross-Presentation of Epitopes Via the Cytosolic Pathway.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2313-2313
Author(s):  
Frank Grünebach ◽  
Markus M. Weck ◽  
Silke Appel ◽  
Daniela Werth ◽  
Christian Sinzger ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Brefeldin A ◽  
Hla Class I ◽  
Class I ◽  
Apoptotic Cells ◽  
Down Regulation ◽  
Cross Presentation ◽  
Hla Class I Molecules ◽  
The Cross ◽  
Mhc Class I Molecules

Abstract Human (h)Dectin-1 is a member of the C-type-lectin-like receptor family that was shown to be the major receptor for fungal β-glucans and to play an important role in cellular responses mediated by these carbohydrates. It is mainly expressed on human DCs and macrophages. In our study, we observed that activation of monocyte-derived dendritic cells (MDCs) with TLR3 ligand (poly I:C) but not with TLR ligand 7/8 (R848) resulted in down-regulation of hDectin-1 expression and this down-regulation correlated with a reduced uptake of apoptotic cells in phagocytosis assays. In order to analyze the possible cross-presentation of engulfed antigens we used CMV infected human fibroblasts (HFF). We found that hDectin-1 is involved in the uptake of CMV-infected HFF leading to cross-presentation of CMV-derived peptides on MHC class I molecules and activation of CMV pp65-specific CD8+ T-lymphocytes. To further delineate the pathway leading to presentation, we pretreated MDCs with compounds that inhibit processing of antigens at defined steps during presentation. Cytosolic protein degradation is performed by the proteasome, a large multicatalytic protease complex. Lactacystin specifically inhibits the 20S and 26S proteasome activity by targeting the catalytic subunit. In standard 51Cr-release assays, addition of lactacystin completely inhibited the presentation of pp65-derived peptides indicating the involvement of the proteasome in these process. The fungal product brefeldin A blocks the MHC class I processing pathway by specifically inhibiting the vesicular egress from the ER and the Golgi complex. In line with previous findings, incubation with brefeldin A almost completely abolished the lysis of MDCs incubated with CMV+ HFF. To further analyze whether the cross-presentation of CMV-derived peptides on HLA class I molecules was dependent on lysosomal proteases, MDCs that were co-incubated with HFF as above were treated with the lysosomotropic agent chloroquine that prevents acidification of the lysosomal compartment involved in the exogenous pathway of antigen presentation. The addition of chloroquine had no effect on the cross-presentation of CMV-derived epitopes on HLA class I-molecules. Summarized, the data reported here show that hDectin-1 functions not only as a pattern recognition receptor in innate immunity but is also involved in the clearing of apoptotic cells and cross-presentation of cellular antigens on MHC class I molecules to specific CTLs.

scholarly journals B7-CD28 costimulation unveils the hierarchy of tumor epitopes recognized by major histocompatibility complex class I-restricted CD8+ cytolytic T lymphocytes.

1996 ◽  
Vol 183 (3) ◽  
pp. 791-800 ◽  
Author(s):  
J V Johnston ◽  
A R Malacko ◽  
M T Mizuno ◽  
P McGowan ◽  
I Hellström ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
Mhc Class I ◽  
Class I ◽  
Cytolytic T Lymphocytes ◽  
Immunodominant Epitope ◽  
Ctl Response ◽  
Histocompatibility Complex ◽  
Cd28 Costimulation ◽  
Mhc Class I Molecules

Immunization of mice with tumors genetically engineered to express the B7 costimulatory molecules amplifies the antitumor immune response mediated by CD8+ cytolytic T lymphocytes (CTL). In this report, we examined the effect of B7-CD28 costimulation on the hierarchy of tumor epitopes. Using a combination of affinity chromatography/reversed-phase high performance liquid chromatography and CTL cloning, we show that major histocompatibility complex (MHC) class I molecules from EL4 lymphoma cells can present at least six distinct CTL epitopes presented by MHC class I molecules. Nevertheless, mice immunized with wild-type B7-negative EL4 cells develop CTL only to one immunodominant epitope. In contrast, immunization with B7-transduced EL4 cells led to not only the amplification of the CTL response to this immunodominant epitope, but also to the recognition of five otherwise silent subdominant epitopes. The adoptive transfer of a CTL clone against such a subdominant epitope cured mice bearing EL4 lymphoma growing as an ascites tumor. The fact that CTL response can be spread to normally silent epitopes as a result of B7-CD28 costimulation suggests a novel approach to manipulate the hierarchy of CTL epitopes and offers an opportunity to explore novel targets for T cell-mediated cancer therapy.

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