Antigen Presenting Cell Extracellular Vesicle Instruction Architecture for Adaptive Immune Activation, Memory Programming, and Therapeutic Engineering

Program Code: HEMOREGEN-IMM-001

Division: HEMOREGEN-IMMUNO

Parent Program: HEMOREGEN-721

Classification: Adaptive Immune Communication Platform

Status: Master Foundational Atlas v1.0

EXECUTIVE SUMMARY

The APC-to-T Cell EV Priming Atlas establishes the foundational communication architecture through which Antigen Presenting Cells (APCs) instruct naïve T cells using extracellular vesicles (EVs).

Within PROJECT HEMOREGEN-721, APC-derived EVs are viewed as biological instruction packets that transfer:

• Antigenic information
• Costimulatory signals
• Metabolic programming
• Differentiation instructions
• Immune memory templates

to initiate and regulate adaptive immunity.

This atlas serves as the foundational framework for:

• Cancer EV vaccines
• Personalized neoantigen vaccines
• Infectious disease vaccines
• T-cell engineering
• Immune memory enhancement
• Precision immunotherapy

SECTION I — APC COMMUNICATION HIERARCHY

Tier 1 — Antigen Acquisition Layer

Primary APC Classes

Tier 2 — Antigen Processing Layer

Sources

Processing Compartments

SECTION II — APC EV BIOGENESIS ARCHITECTURE

Stage 1

Threat Recognition

Pattern Recognition Systems

Outcome:

APC activation.

Stage 2

Signal Integration

Activated Pathways:

• NF-κB
• STAT1
• STAT3
• IRF3
• IRF7

Outcome:

EV biogenesis induction.

Stage 3

Polarized EV Production

EV Classes:

SECTION III — APC EV CARGO ATLAS

Cargo Class A

Antigenic Instruction Layer

Cargo Class B

Costimulatory Layer

Cargo Class C

Cytokine Programming Layer

Cargo Class D

Regulatory RNA Layer

Cargo Class E

Metabolic Programming Layer

SECTION IV — EV ADDRESSING AND TARGETING SYSTEM

Address Layer A

Synapse Docking Architecture

Purpose:

Physical stabilization.

Address Layer B

Antigen Recognition Code

Determines:

• Specificity
• Clonal selection
• Immune memory potential

Address Layer C

Costimulation Authorization Code

Purpose:

Prevent anergy.

SECTION V — T CELL DIFFERENTIATION ATLAS

TH1 Program

APC EV Signature

• IL-12
• IFN-associated signals
• miR-155

Outcome:

Cell-mediated immunity.

Applications:

• Viral infection
• Cancer immunity

TH2 Program

APC EV Signature

• IL-4
• IL-13-supportive cargo

Outcome:

Humoral immunity.

TH17 Program

APC EV Signature

• IL-6
• TGFβ

Outcome:

Barrier defense.

TFH Program

APC EV Signature

• IL-21
• CXCR5-associated programming

Outcome:

Germinal center development.

TREG Program

APC EV Signature

• IL-10
• TGFβ
• miR-146a

Outcome:

Tolerance induction.

SECTION VI — APC → CD8 CROSS-PRIMING NETWORK

Phase 1

Antigen Transfer

Cargo:

• MHC-I peptide complexes

Phase 2

Activation

Cargo:

• CD80
• CD86
• IL-12

Phase 3

Expansion

Cargo:

• IL-2-associated signals
• miR-21

Phase 4

Effector Programming

Cargo:

• Cytotoxic differentiation modules

Phase 5

Memory Formation

Cargo:

• BCL6-associated regulators
• Epigenetic programming factors

SECTION VII — IMMUNE MEMORY PROGRAMMING ARCHITECTURE

Short-Term Memory

Characteristics:

• Rapid recall
• Effector dominance

Central Memory

Characteristics:

• Long persistence
• Secondary expansion potential

Tissue Resident Memory

Characteristics:

• Local protection
• Barrier immunity

EV Memory Cargo

SECTION VIII — APC EV FAILURE ATLAS

Failure Type 1

Antigen Loading Defect

Outcome:

Poor immunity.

Failure Type 2

Costimulation Defect

Outcome:

Anergy.

Failure Type 3

Checkpoint Dominance

Outcome:

T-cell exhaustion.

Failure Type 4

Tolerance Leakage

Outcome:

Autoimmunity.

Failure Type 5

EV Cargo Degradation

Outcome:

Reduced signaling fidelity.

SECTION IX — HEMOREGEN BIOMARKER PANEL

APC Identity Markers

• CD11c
• HLA-DR
• CD80
• CD86

EV Identity Markers

• CD9
• CD63
• CD81

Activation Markers

• IL-12
• IFN-related proteins
• CD40

RNA Biomarkers

• miR-155
• miR-146a
• miR-21
• miR-181a

Memory Biomarkers

• TCF1-associated cargo
• BCL6-associated cargo

SECTION X — HEMOREGEN THERAPEUTIC ENGINEERING BLUEPRINT

HEM-RX-001A

Cancer Neoantigen APC-EV Vaccine Platform

Purpose:

Patient-specific oncology vaccines.

HEM-RX-001B

Universal Viral APC-EV Vaccine Platform

Purpose:

Rapid outbreak response.

HEM-RX-001C

Memory-Amplifying APC-EV Platform

Purpose:

Long-duration immunity.

HEM-RX-001D

Tolerance-Inducing APC-EV Platform

Purpose:

Autoimmune disease modulation.

HEM-RX-001E

Synthetic Programmable APC-EV Platform

Purpose:

Precision immune programming.

SECTION XI — SCF FIVE PRINCIPLE ALIGNMENT

TRANSLATIONAL DEVELOPMENT ROADMAP

H1 — Mapping

• APC cargo atlas
• EV address atlas
• T-cell response atlas

H2 — Validation

• Human PBMC systems
• Organoid models
• Antigen-specific assays

H3 — Engineering

• Vaccine EV platforms
• Memory EV platforms
• Personalized oncology EVs

H4 — Biomarker Development

• Companion diagnostics
• Vaccine response monitoring

H5 — Clinical Translation

• IND-enabling studies
• First-in-human APC-EV vaccines
• Precision immunotherapy programs

MASTER REGISTRY INDEX

HEMOREGEN-IMM-001 — APC-to-T Cell EV Priming Atlas

HEM-RX-001 — Engineered APC-EV Vaccine Platform

HEM-RX-001A — Cancer Neoantigen APC-EV Vaccine Platform

HEM-RX-001B — Universal Viral APC-EV Vaccine Platform

HEM-RX-001C — Memory-Amplifying APC-EV Platform

HEM-RX-001D — Tolerance-Inducing APC-EV Platform

HEM-RX-001E — Synthetic Programmable APC-EV Platform

HEMOREGEN-721-PROG-0001 — Project HEMOREGEN-721 Master Program

SCF-IMM-PRIME-0001 — APC Immune Priming Systems Atlas

SCF-IMM-MEMORY-0001 — EV-Mediated Adaptive Immune Memory Architecture