HLA-A1

Human leukocyte antigens (HLAs) are proteins encoded by genes on chromosome 6 that help the immune system recognize and respond to foreign threats. 

As part of the major histocompatibility complex (MHC), HLAs, including HLA-A1, play critical roles in immune defense, organ transplantation, and disease susceptibility.

What Are HLAs?

The human leukocyte antigen (HLA) system is a group of genes found on chromosome 6 that helps the immune system recognize and respond to foreign substances like viruses and cancer cells. HLAs are the human version of a larger group of proteins called the major histocompatibility complex (MHC).

There are three main types of HLA genes:

Class I (HLA-A, -B, -C)

Class I HLA proteins are found on almost all cells in the body and present pieces of proteins (called peptides) to CD8+ T cells, a type of immune cell that can destroy infected or damaged cells. HLA-A1 is a part of the Class I group of proteins.

Class II (HLA-DR, -DP, -DQ)

Class II HLAs are found on immune cells like B cells and macrophages, and participate in immune system activation by presenting peptides to CD4+ helper T cells.

Class III

Class III genes make proteins involved in other immune functions, but they don't present peptides.

HLAs are highly variable between individuals, which makes them essential for immune defense—but also makes organ matching for transplantation more complicated.

What Is HLA-A1?

HLA-A1 is a specific allele of the HLA-A gene, which is part of the class I HLA group. Like other class I proteins, it helps the immune system detect and respond to problems inside the body’s own cells, such as viral infections or cancer.

What Does the HLA-A1 Protein Do?

The HLA-A1 protein sits on the surface of nearly all nucleated cells. It’s made up of:

• A heavy alpha chain, and
• A helper protein called β2-microglobulin.

Together, these form a structure that holds short pieces of protein (8–10 amino acids long) and shows them to CD8+ T cells. If these peptides come from a virus or cancer cell, the T cell will attack the infected or abnormal cell.

HLA-A1 also interacts with natural killer (NK) cells, which are another part of the immune system. If a cell stops displaying HLA-A1 (as some cancer or virus-infected cells do), NK cells may destroy it.

When Is HLA-A1 Testing Useful?

HLA-A1 testing may be useful in the following scenarios: 

Transplant Matching

HLA-A1 testing is part of routine HLA typing for patients needing an organ or bone marrow transplant. Mismatches at the HLA-A gene can lead to graft rejection or graft-versus-host disease (GVHD).

Disease Risk

Some diseases are linked to specific HLA types. HLA-A1 is often part of a genetic pattern called the A1-B8-DR3 haplotype, which has been associated with:

• Celiac disease
• Graves' disease
• Systemic lupus erythematosus (SLE)
• Multiple sclerosis
• Type 1 diabetes

These links vary depending on the population and are not always fully understood.

Infection Resistance

HLA-A1 may affect how the body responds to certain infections. One study found that people with two copies of HLA-A1 may resist influenza virus replication inside their immune cells, possibly offering some protection.

Transfusion and Alloimmunization

Patients can form antibodies against HLA-A1 after transfusions, pregnancies, or transplants. These antibodies can:

• Interfere with platelet transfusions,
• Lead to transplant rejection, or
• Make it harder to find compatible donors in the future.

Research and Past Use in Paternity Testing

Before modern DNA testing, HLA types (like HLA-A1) were used to help with paternity testing. Today, HLA typing is more commonly used in research on the immune system and disease.

HLA Typing: Test Procedures

HLA typing is performed to identify a patient's human leukocyte antigen profile for transplantation matching, disease association studies, and antibody screening. There are three main types of HLA testing. 

Serologic Testing

Serologic typing is the classical method, using peripheral blood lymphocytes as the sample. 

In this approach, lymphocytes are exposed to a panel of HLA-specific antisera in microplates, and the presence of antigen-antibody binding is determined by complement-mediated cell lysis. 

Molecular HLA Typing

Molecular HLA typing is now the standard, providing high-resolution identification of specific HLA alleles. 

It uses DNA extracted from blood or buccal cells. It involves techniques such as sequence-specific oligonucleotide probes (SSOP), sequence-specific primers (SSP), or direct DNA sequencing to detect allele-level differences, particularly important in bone marrow and stem cell transplantation. 

HLA Antibody Screening and Crossmatching

HLA antibody screening and crossmatching detect preformed antibodies that may interfere with transplantation. 

This testing uses the patient's serum and is typically performed using microlymphocytotoxicity assays, flow cytometry, or Luminex®-based bead technology. Together, these tests support donor matching, predict immune compatibility, and reduce the risk of transplant rejection.

What Does It Mean to Have HLA-A1?

If someone has HLA-A1, they inherited this specific version of the HLA-A gene. This can:

• Help with finding a compatible organ or bone marrow donor
• Influence how the immune system responds to infections or treatments

In rare cases, having two copies of HLA-A1 may give added resistance to certain viruses.

What If Someone Doesn’t Have HLA-A1?

If a person does not have HLA-A1, they simply have other versions of the HLA-A gene. This is normal and doesn't cause any health problems by itself. However, their different HLA type may:

• Affect transplant compatibility
• Be linked to different disease risks in some populations

Advances in Research: Why HLA-A1 Matters in Transplant Science

Scientists have identified key parts of the HLA-A1 protein that are recognized by antibodies. One important part is the amino acid lysine at position 44 (44K). This discovery helps doctors predict which HLA mismatches are more likely to cause immune reactions, such as rejection of a transplanted organ.

Understanding these "eplets" (small protein segments involved in immune recognition) may help improve the safety of transplants by identifying donors who are a better match.

Summary for Clinicians

HLA-A1 is a class I HLA allele involved in presenting peptide antigens to CD8+ T cells and regulating NK cell responses.

It plays key roles in transplantation, autoimmune diseases, viral immunity, and transfusion reactions.

HLA-A1 is part of common haplotypes (like A1-B8-DR3) and contributes to individual differences in immune response.

Typing for HLA-A1 is routine in transplant workups and is gaining importance in precision immunology and disease risk prediction.