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- EMDB-46602: CryoEM structure of anti-MHC-I Fab B1.23.2 complex with HLA-B44:05 -

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Entry
Database: EMDB / ID: EMD-46602
TitleCryoEM structure of anti-MHC-I Fab B1.23.2 complex with HLA-B44:05
Map datamain map file
Sample
  • Complex: Complex of Anti-human-mAb B1.23.2 Fab and MHC-I HLA-B44:05
    • Protein or peptide: HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05)
    • Protein or peptide: Beta-2-microglobulin
    • Protein or peptide: B1.23.2 Fab Heavy Chain: CH and CH1 domains
    • Protein or peptide: B1.23.2 Fab Light Chain: VL and C kappa domains
    • Protein or peptide: MHC class II antigen peptide
KeywordsMHC-I / anti-human-mAb / H2-Dd / B1.23.2 / Fab / anti-MHC-I antibody / anti-tumor / cancer immunotherapy / IMMUNE SYSTEM
Function / homology
Function and homology information


antigen processing and presentation of peptide or polysaccharide antigen via MHC class II / antigen processing and presentation of peptide antigen via MHC class I / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / negative regulation of iron ion transport / lumenal side of endoplasmic reticulum membrane / T cell mediated cytotoxicity ...antigen processing and presentation of peptide or polysaccharide antigen via MHC class II / antigen processing and presentation of peptide antigen via MHC class I / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / negative regulation of iron ion transport / lumenal side of endoplasmic reticulum membrane / T cell mediated cytotoxicity / cellular response to iron(III) ion / negative regulation of forebrain neuron differentiation / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / transferrin transport / regulation of iron ion transport / regulation of erythrocyte differentiation / negative regulation of receptor-mediated endocytosis / HFE-transferrin receptor complex / response to molecule of bacterial origin / MHC class I peptide loading complex / cellular response to iron ion / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / MHC class I protein complex / peptide antigen assembly with MHC class II protein complex / negative regulation of neurogenesis / positive regulation of receptor-mediated endocytosis / cellular response to nicotine / MHC class II protein complex / positive regulation of T cell mediated cytotoxicity / multicellular organismal-level iron ion homeostasis / specific granule lumen / peptide antigen binding / antigen processing and presentation of exogenous peptide antigen via MHC class II / phagocytic vesicle membrane / positive regulation of immune response / recycling endosome membrane / Interferon gamma signaling / positive regulation of T cell activation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / negative regulation of epithelial cell proliferation / Modulation by Mtb of host immune system / sensory perception of smell / positive regulation of cellular senescence / tertiary granule lumen / DAP12 signaling / MHC class II protein complex binding / T cell differentiation in thymus / late endosome membrane / negative regulation of neuron projection development / ER-Phagosome pathway / protein refolding / early endosome membrane / amyloid fibril formation / protein homotetramerization / intracellular iron ion homeostasis / adaptive immune response / learning or memory / endoplasmic reticulum lumen / Amyloid fiber formation / Golgi membrane / external side of plasma membrane / lysosomal membrane / focal adhesion / Neutrophil degranulation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / endoplasmic reticulum / Golgi apparatus / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol
Similarity search - Function
MHC class II, alpha chain, N-terminal / Class II histocompatibility antigen, alpha domain / Class II histocompatibility antigen, alpha domain / MHC class II, alpha/beta chain, N-terminal / MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily ...MHC class II, alpha chain, N-terminal / Class II histocompatibility antigen, alpha domain / Class II histocompatibility antigen, alpha domain / MHC class II, alpha/beta chain, N-terminal / MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / : / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Beta-2-microglobulin / MHC class I antigen / MHC class II antigen
Similarity search - Component
Biological speciesHomo sapiens (human) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.31 Å
AuthorsJiang J / Natarajan K / Margulies DH / Lei H / Huang R
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)Intramural United States
CitationJournal: Commun Biol / Year: 2026
Title: Structural mechanism of anti-MHC-I antibody blocking of inhibitory NK cell receptors in tumor immunity.
Authors: Jiansheng Jiang / Abir K Panda / Kannan Natarajan / Haotian Lei / Shikha Sharma / Lisa F Boyd / Reanne R Towler / Sruthi Chempati / Javeed Ahmad / Abraham J Morton / Zabrina C Lang / Yi Sun ...Authors: Jiansheng Jiang / Abir K Panda / Kannan Natarajan / Haotian Lei / Shikha Sharma / Lisa F Boyd / Reanne R Towler / Sruthi Chempati / Javeed Ahmad / Abraham J Morton / Zabrina C Lang / Yi Sun / Nikolaos Sgourakis / Martin Meier-Schellersheim / Rick K Huang / Ethan M Shevach / David H Margulies /
Abstract: Anti-major histocompatibility complex class I (MHC-I) mAbs can stimulate immune responses to tumors and infections by blocking suppressive signals delivered via various immune inhibitory receptors. ...Anti-major histocompatibility complex class I (MHC-I) mAbs can stimulate immune responses to tumors and infections by blocking suppressive signals delivered via various immune inhibitory receptors. To understand such functions, we determined the structure of a highly cross-reactive anti-human MHC-I mAb, B1.23.2, in complex with the MHC-I molecule HLA-B*44:05 by both cryo-electron microscopy (cryo-EM) and X-ray crystallography. Structural models determined by the two methods were essentially identical revealing that B1.23.2 binds a conserved region on the α2 helix that overlaps the killer immunoglobulin-like receptor (KIR) binding site. Structural comparison to KIR/HLA complexes reveals a mechanism by which B1.23.2 blocks inhibitory receptor interactions, leading to natural killer (NK) cell activation. B1.23.2 treatment of the human KLM-1 pancreatic cancer model in humanized (NSG-IL15) mice provides evidence of suppression of tumor growth. Such anti-MHC-I mAb that block inhibitory KIR/HLA interactions may prove useful for tumor immunotherapy.
History
DepositionAug 16, 2024-
Header (metadata) releaseFeb 11, 2026-
Map releaseFeb 11, 2026-
UpdateFeb 11, 2026-
Current statusFeb 11, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46602.png

Downloads & links

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Map

FileDownload / File: emd_46602.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmain map file
Projections & slices

Image control

Size
Brightness
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AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 256 pix.
= 212.48 Å		0.83 Å/pix.
x 256 pix.
= 212.48 Å		0.83 Å/pix.
x 256 pix.
= 212.48 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.06
Minimum - Maximum-0.32089546 - 0.46102092
Average (Standard dev.)0.0007658819 (±0.010544277)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 212.48 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_46602_msk_1.map
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AxesZYX

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Half map: half map A

Fileemd_46602_half_map_1.map
Annotationhalf map A
Projections & Slices
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Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_46602_half_map_2.map
Annotationhalf map B
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Sample components

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Entire : Complex of Anti-human-mAb B1.23.2 Fab and MHC-I HLA-B44:05

EntireName: Complex of Anti-human-mAb B1.23.2 Fab and MHC-I HLA-B44:05
Components
  • Complex: Complex of Anti-human-mAb B1.23.2 Fab and MHC-I HLA-B44:05
    • Protein or peptide: HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05)
    • Protein or peptide: Beta-2-microglobulin
    • Protein or peptide: B1.23.2 Fab Heavy Chain: CH and CH1 domains
    • Protein or peptide: B1.23.2 Fab Light Chain: VL and C kappa domains
    • Protein or peptide: MHC class II antigen peptide

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Supramolecule #1: Complex of Anti-human-mAb B1.23.2 Fab and MHC-I HLA-B44:05

SupramoleculeName: Complex of Anti-human-mAb B1.23.2 Fab and MHC-I HLA-B44:05
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Details: The sample was mixed 1:1 mole ratio of B1.23.2 Fab and HLA-B44 and purified. with concentration of 1.0 mg/ml
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 88.943 KDa

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Macromolecule #1: HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05)

MacromoleculeName: HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05)
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 31.802119 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: GSHSMRYFYT AMSRPGRGEP RFITVGYVDD TLFVRFDSDA TSPRKEPRAP WIEQEGPEYW DRETQISKTN TQTYRENLRT ALRYYNQSE AGSHIIQRMY GCDVGPDGRL LRGYDQYAYD GKDYIALNED LSSWTAADTA AQITQRKWEA ARVAEQDRAY L EGLCVESL ...String:
GSHSMRYFYT AMSRPGRGEP RFITVGYVDD TLFVRFDSDA TSPRKEPRAP WIEQEGPEYW DRETQISKTN TQTYRENLRT ALRYYNQSE AGSHIIQRMY GCDVGPDGRL LRGYDQYAYD GKDYIALNED LSSWTAADTA AQITQRKWEA ARVAEQDRAY L EGLCVESL RRYLENGKET LQRADPPKTH VTHHPISDHE VTLRCWALGF YPAEITLTWQ RDGEDQTQDT ELVETRPAGD RT FQKWAAV VVPSGEEQRY TCHVQHEGLP KPLTLRW

UniProtKB: MHC class I antigen

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Macromolecule #2: Beta-2-microglobulin

MacromoleculeName: Beta-2-microglobulin / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.879356 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString:
MIQRTPKIQV YSRHPAENGK SNFLNCYVSG FHPSDIEVDL LKNGERIEKV EHSDLSFSKD WSFYLLYYTE FTPTEKDEYA CRVNHVTLS QPKIVKWDRD M

UniProtKB: Beta-2-microglobulin

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Macromolecule #3: B1.23.2 Fab Heavy Chain: CH and CH1 domains

MacromoleculeName: B1.23.2 Fab Heavy Chain: CH and CH1 domains / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.845555 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLQQSGTV LARPGSSVKM SCKASGYSFT SYWMHWVKQR PGQGLEWIGA IYPGNSDATY NQKFKGKAKL TAVTSANTAY MELSSLTNE DSAVYYCTNY FDQWGQGTTL TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP VTVSWNSGAL T SGVHTFPA ...String:
QVQLQQSGTV LARPGSSVKM SCKASGYSFT SYWMHWVKQR PGQGLEWIGA IYPGNSDATY NQKFKGKAKL TAVTSANTAY MELSSLTNE DSAVYYCTNY FDQWGQGTTL TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP VTVSWNSGAL T SGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPK

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Macromolecule #4: B1.23.2 Fab Light Chain: VL and C kappa domains

MacromoleculeName: B1.23.2 Fab Light Chain: VL and C kappa domains / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.846432 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQTPSS MYASLGERVT ITCKASQDIN SYLNWFQLKP GKSPKTLIYR ANRLVDGVPS RFSGSGSGQD YSLTISSLEY EDMGIYYCL QYDELYTFGG GTKLEMKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK ...String:
DIQMTQTPSS MYASLGERVT ITCKASQDIN SYLNWFQLKP GKSPKTLIYR ANRLVDGVPS RFSGSGSGQD YSLTISSLEY EDMGIYYCL QYDELYTFGG GTKLEMKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK DSTYSMSSTL TLTKDEYERH NSYTCEATHK TSTSPIVKSF NRNEC

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Macromolecule #5: MHC class II antigen peptide

MacromoleculeName: MHC class II antigen peptide / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 1.090165 KDa
SequenceString:
EEFGRAFSF

UniProtKB: MHC class II antigen

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1.0 mg/mL
BufferpH: 8 / Component - Concentration: 0.25 mg/ml / Component - Name: TBS
GridModel: EMS Lacey Carbon / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 1200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
TemperatureMin: 78.0 K / Max: 80.0 K
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: SUPER-RESOLUTION / Number grids imaged: 1 / Number real images: 3077 / Average exposure time: 8.0 sec. / Average electron dose: 54.2 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Calibrated magnification: 60096 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 105000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 662994
CTF correctionSoftware - Name: cryoSPARC (ver. 4.4.1) / Details: PATCH CTF estimation / Type: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8tq6

Final reconstructionNumber classes used: 48 / Applied symmetry - Point group: C1 (asymmetric) / Algorithm: SIMULTANEOUS ITERATIVE (SIRT) / Resolution.type: BY AUTHOR / Resolution: 3.31 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.4.1) / Number images used: 406992
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
Final 3D classificationNumber classes: 48 / Software - Name: cryoSPARC (ver. 4.4.1)
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

8tq6


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Protocol: RIGID BODY FIT / Overall B value: 128.8 / Target criteria: CC
Output model

PDB-9d74:
CryoEM structure of anti-MHC-I Fab B1.23.2 complex with HLA-B44:05

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