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- EMDB-46601: CryoEM structure of anti-MHC-I mAb B1.23.2 complex with HLA-B44:05 -

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Entry
Database: EMDB / ID: EMD-46601
TitleCryoEM structure of anti-MHC-I mAb B1.23.2 complex with HLA-B44:05
Map datamai map file
Sample
  • Complex: Complex of Anti-human-mAb B1.23.2 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: MHC class II antigen peptide
    • Protein or peptide: B1.23.2 mAb Heavy Chain: Full-length
    • Protein or peptide: B1.23.2 Light Chain: VL and C kappa domains
KeywordsMHC-I / anti-human-mAb / H2-Dd / B1.23.2 / anti-MHC-I antibody / anti-tumor / cancer immunotherapy / ANTITUMOR PROTEIN / ANTITUMOR PROTEIN-Immune System complex
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 / T cell mediated cytotoxicity / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / regulation of iron ion transport ...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 / T cell mediated cytotoxicity / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / regulation of iron ion transport / cellular response to iron(III) ion / negative regulation of iron ion transport / 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 / regulation of erythrocyte differentiation / response to molecule of bacterial origin / MHC class I peptide loading complex / HFE-transferrin receptor complex / transferrin transport / cellular response to iron ion / negative regulation of receptor-mediated endocytosis / 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 / cellular response to nicotine / positive regulation of receptor-mediated endocytosis / 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 / negative regulation of epithelial cell proliferation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / 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 exosome / extracellular region / membrane / identical protein binding / 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: 3.02 Å
AuthorsJiang J / Natarajan K / Lei H / Huang R / Margulies DH
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 4, 2026-
Map releaseFeb 4, 2026-
UpdateMar 18, 2026-
Current statusMar 18, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46601.png

Downloads & links

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Map

FileDownload / File: emd_46601.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmai map file
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 288 pix.
= 239.04 Å		0.83 Å/pix.
x 288 pix.
= 239.04 Å		0.83 Å/pix.
x 288 pix.
= 239.04 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.2950346 - 0.5683547
Average (Standard dev.)0.0006791331 (±0.011723799)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 239.04 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_46601_msk_1.map
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AxesZYX

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Half map: half map A

Fileemd_46601_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_46601_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 and MHC-I HLA-B44:05

EntireName: Complex of Anti-human-mAb B1.23.2 and MHC-I HLA-B44:05
Components
  • Complex: Complex of Anti-human-mAb B1.23.2 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: MHC class II antigen peptide
    • Protein or peptide: B1.23.2 mAb Heavy Chain: Full-length
    • Protein or peptide: B1.23.2 Light Chain: VL and C kappa domains

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

SupramoleculeName: Complex of Anti-human-mAb B1.23.2 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 antibody and HLA-B44 and purified. with concentration of 1.0 mg/ml
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 196.472 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: MHC class II antigen peptide

MacromoleculeName: MHC class II antigen peptide / type: protein_or_peptide / ID: 3 / 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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Macromolecule #4: B1.23.2 mAb Heavy Chain: Full-length

MacromoleculeName: B1.23.2 mAb Heavy Chain: Full-length / type: protein_or_peptide / ID: 4
Details: B1.23.2 mAb VH, CH1 of human IgG1, and CH2, CH3 domains, including the hinge (213-226) and LALAPG mutations (A230, A231, and G325)
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 48.506445 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 KKVEPKSCDK THTCPPCPAP EAAGGPSVFL FP PKPKDTL MISRTPEVTC VVVDVSHEDP EVKFNWYVDG VEVHNAKTKP REEQYNSTYR VVSVLTVLHQ DWLNGKEYKC KVS NKALGA PIEKTISKAK GQPREPQVYT LPPSREEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSF FLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK

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Macromolecule #5: B1.23.2 Light Chain: VL and C kappa domains

MacromoleculeName: B1.23.2 Light Chain: VL and C kappa domains / type: protein_or_peptide / ID: 5 / 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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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 (6k x 4k) / Detector mode: SUPER-RESOLUTION / Number grids imaged: 1 / Number real images: 7154 / Average exposure time: 2.5 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: 664724
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: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.4.1) / Number images used: 359876
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
Final 3D classificationNumber classes: 41 / 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-9d73:
CryoEM structure of anti-MHC-I mAb B1.23.2 complex with HLA-B44:05

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