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Human Leukocyte Antigen Analysis – Gene Expression and HLA Biomarkers

What is human leukocyte antigen and why is it important?

Human leukocyte antigen analysis focuses on the study of HLA molecules, a group of proteins encoded by the major histocompatibility complex (MHC) located on chromosome 6.

HLA molecules play a central role in the immune system by presenting peptide fragments to T cells, enabling the recognition of pathogens and abnormal cells. This mechanism is essential for adaptive immunity, immune surveillance, and self/non-self discrimination.

HLA variability is a key determinant of immune responses, influencing susceptibility to diseases, transplant compatibility, and responses to immunotherapies.

AnyGenes array for analyzing Human Leukocyte Antigens (HLA) for immune response research.

Human leukocyte antigen analysis relies on gene expression-based approaches to study antigen presentation and immune activation pathways.

Human leukocyte antigen biomarker list
Explore the key genes involved in HLA-mediated antigen presentation and immune regulation.
View the full biomarker list
.

Overview of different types of Human Leukocyte Antigens (HLA) and their significance in immune response and transplantation.

Map of the human HLA

The complex is conventionally divided into three regions: I, II, and III. Each region contains numerous loci (genes), only some of which are shown. Abbreviations: tapasin (TAPBP); large multifunctional proteases 1 and 2 (LMP1 and LMP2 respectively); transporter associated with antigen processing 1 and 2 (TAP1 and TAP2 respectively); complement components 2, 4A and 4B (C2C4A and C4B respectively); complement factor B (BF); heat-shock protein 1A A-type, heat-shock protein 1A B-type, and heat-shock protein 1A–like (HSPA1AHSPA1B and HSPA1L respectively); lymphotoxins A and B (LTA and LTB respectively); tumor necrosis factor α (TNF-α); major histocompatibility complex class I chain genes A and B (MICA and MICB respectively) (graphic from Castiblanco J, Anaya JM. 2015).

Human leukocyte antigen analysis: key takeaways

  • Central role in antigen presentation and immune recognition
  • Essential for transplantation compatibility
  • Highly polymorphic system influencing disease susceptibility
  • Strongly connected to immune regulation pathways
  • Suitable for gene expression-based biomarker analysis

When to perform human leukocyte antigen analysis?

Human leukocyte antigen analysis is essential in multiple research and clinical contexts.

It is commonly used to:

  • evaluate antigen presentation mechanisms
  • study immune responses in infection and inflammation
  • assess donor-recipient compatibility
  • identify biomarkers in cancer immunotherapy
  • investigate autoimmune diseases

HLA classes and biological function

Class I HLA molecules

(HLA-A, HLA-B, HLA-C)
Present endogenous antigens to CD8+ T cells and enable elimination of infected or tumor cells.

Class II HLA molecules

(HLA-DP, HLA-DQ, HLA-DR)
Expressed on antigen-presenting cells, they present exogenous antigens to CD4+ T cells and regulate immune responses.

Key genes involved in dendritic cell profiling

The HLA region is functionally connected to broader immune regulation pathways, including cytokine signaling and immune checkpoint mechanisms.

Immune checkpoints

CD274 (PD-L1), PDCD1, PDCD1LG2, CTLA4, LAG3, HAVCR2, CD276, VTCN1

Co-stimulatory molecules

CD80, CD86, CD28, ICOS, ICOSLG, CD40, CD40LG, TNFRSF4, TNFRSF9, TNFRSF14, CD27, CD70, TNFSF4, TNFSF9, TNFSF14

Cytokines and chemokines

IL1A, IL2, IL4, IL5, IL6, IL10, IL12B, IL13, IL17A, IL18, IFNG, IFNB1, TNF, TGFB1, CCL5, CXCL9

Immune signaling pathways

AKT1, STAT3, PIK3CA, NFKBIL1

Immune receptors and regulators

BTLA, LILRB1, KIR3DL1, CD160, KLRG1, CD244, NCR3

Immunometabolism and suppression

IDO1, ENTPD1, NT5E, ADORA2A

Additional HLA locus-associated genes

HSPA1A, HSPA1B, HSPA1L, TAP1, TAP2, SKIV2L, NOTCH4, TRIM39, RNF39, AIF1, BTNL2, DAXX, HSD17B8, GNL1, ALK, C6orf10, OR2H2, TUBB

How to perform human leukocyte antigen analysis?

Analyzing HLA pathways can be challenging due to the high polymorphism and complexity of the MHC region.

Gene expression profiling for HLA analysis

Human leukocyte antigen analysis is commonly performed using gene expression profiling approaches to evaluate antigen presentation and immune activation.

Transcriptomic methods provide a global overview of gene expression patterns across HLA-related pathways.

qPCR-based human leukocyte antigen analysis

qPCR-based approaches provide targeted and highly reproducible measurement of HLA-related genes, enabling precise analysis of antigen presentation pathways.

This approach is particularly relevant for focused studies and limited sample availability.

Workflow:

  1. Select relevant HLA and immune-related genes
  2. Measure gene expression using qPCR or transcriptomic methods
  3. Normalize data
  4. Compare expression profiles

Key considerations:

  • Selecting targeted gene panels is essential to focus on relevant biomarkers and reduce variability
  • Targeted qPCR approaches enable robust, reproducible, and sensitive HLA analysis
  • Customized qPCR panels allow precise investigation of antigen presentation and immune regulation pathways
  • Compared to transcriptomic approaches, targeted qPCR provides faster, cost-effective, and reproducible results

Human leukocyte antigen analysis in disease and research

Transplantation

HLA matching is critical to reduce rejection risk and improve graft survival.

Autoimmune diseases

Specific HLA alleles are associated with diseases such as rheumatoid arthritis and type 1 diabetes.

Infectious diseases

HLA variability influences susceptibility to infections such as HIV and tuberculosis.

Cancer immunotherapy

HLA molecules regulate antigen presentation and influence responses to immunotherapies.

Therapeutic applications of human leukocyte antigen analysis

  • transplant compatibility analysis
  • biomarker discovery
  • immunotherapy research
  • vaccine development
  • immune monitoring

Why perform HLA analysis with AnyGenes®?

Studying HLA pathways requires reliable gene expression tools.

AnyGenes® supports researchers with customized qPCR panels designed for HLA pathway analysis and immune profiling.

Key advantages:

  • flexible gene panel design
  • pathway-focused selection
  • high reproducibility
  • standardized workflows

These solutions are widely used in immunology and translational research.

Analyze your pathway data with AnyGenes® software

Scientific data is only as powerful as the analysis behind it.

AnyGenes® provides a dedicated data analysis tool specifically developed for SignArrays® pathway panels.

What does it allow you to do?

  • Automated ΔCq calculation
  • Normalization with selected housekeeping genes
  • Comparison of up to 10 experimental conditions
  • Generation of descriptive statistics
  • Publication-ready graphs
  • Exportable tables for manuscripts and presentations

Developed on Excel (compatible with 2007+), the software is user-friendly and requires no advanced bioinformatics skills.

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to initiate your project.

Frequently asked questions

What is human leukocyte antigen (HLA)?

HLA refers to a group of proteins responsible for antigen presentation and immune recognition.

How to perform human leukocyte antigen analysis?

HLA analysis is typically performed using gene expression profiling and qPCR-based approaches to evaluate antigen presentation and immune activation.

Which tools are used for HLA analysis?

qPCR arrays, transcriptomic methods, and targeted gene panels are commonly used.

Why are HLA biomarkers important?

They help understand immune responses, disease susceptibility, and transplant compatibility.

Which genes are involved in HLA analysis?

Key genes include HLA class I and II molecules and antigen processing genes such as TAP1 and TAP2.

How can HLA pathways be analyzed?

HLA pathways can be studied using gene expression profiling techniques such as qPCR.

Human leukocyte antigen biomarker list

You can check the biomarker list included in this pathway, see below:

Looking for more answers? Visit our Help & FAQ section to find detailed information about our products, services, and technical support.

Bibliography

1. Medhasi S, Chantratita N. Human Leukocyte Antigen (HLA) System: Genetics and Association with Bacterial and Viral Infections. J Immunol Res. (2022)26;2022:9710376..

2. Wang C, et al. Human leukocyte antigen (HLA) and cancer immunotherapy: HLA-dependent and -independent adoptive immunotherapies. (2020).

3. Crux NB, Elahi S. Human Leukocyte Antigen (HLA) and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections? Front Immunol. (2017)18:8:832.

4. Zhang GL, et al. Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High-Throughput Oligonucleotide Probe Array Analysis. Front Immunol. (2014)27;5:597.

5. Cruz-Tapias P, et al. Chapter 10: Major histocompatibility complex: Antigen processing and presentation.

6. Castiblanco J, Anaya JM. Genetics and Vaccines in the Era of Personalized Medicine.Curr Genomics. (2015)16(1):47–59.

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