HLA-B — Major Histocompatibility Complex Class I B

HLA-B — Major Histocompatibility Complex Class I B

<div class="infobox infobox-gene">
<div class="infobox-header">HLA-B</div>
<table class="infobox-data">
<tr><th>Gene Symbol</th><td>HLA-B</td></tr>
<tr><th>Full Name</th><td>Major Histocompatibility Complex Class I B</td></tr>
<tr><th>Chromosomal Location</th><td>6p21.3</td></tr>
<tr><th>NCBI Gene ID</th><td><a href="https://www.ncbi.nlm.nih.gov/gene/3135" target="_blank">3135</a></td></tr>
<tr><th>OMIM</th><td><a href="https://www.omim.org/entry/142830" target="_blank">142830</a></td></tr>
<tr><th>Ensembl ID</th><td><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000206428" target="_blank">ENSG00000206428</a></td></tr>
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/P01889" target="_blank">P01889</a></td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, ALS, Stroke</td></tr>
<tr><th>Expression</th><td>All nucleated cells, microglia, immune cells</td></tr>
</table>
</div>

Overview

HLA-B (Major Histocompatibility Complex Class I B) is a gene located on chromosome 6p21.3 that encodes the 44 kDa heavy chain of the HLA class I molecule. HLA-B is one of the most polymorphic genes in the human genome, with over 6,000 known alleles[@klein2000]. It plays a critical role in adaptive immune surveillance by presenting endogenously synthesized peptide antigens to CD8+ cytotoxic T lymphocytes, enabling recognition and elimination of infected or abnormal cells[@shiina2009].

HLA-B — Major Histocompatibility Complex Class I B

<div class="infobox infobox-gene">
<div class="infobox-header">HLA-B</div>
<table class="infobox-data">
<tr><th>Gene Symbol</th><td>HLA-B</td></tr>
<tr><th>Full Name</th><td>Major Histocompatibility Complex Class I B</td></tr>
<tr><th>Chromosomal Location</th><td>6p21.3</td></tr>
<tr><th>NCBI Gene ID</th><td><a href="https://www.ncbi.nlm.nih.gov/gene/3135" target="_blank">3135</a></td></tr>
<tr><th>OMIM</th><td><a href="https://www.omim.org/entry/142830" target="_blank">142830</a></td></tr>
<tr><th>Ensembl ID</th><td><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000206428" target="_blank">ENSG00000206428</a></td></tr>
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/P01889" target="_blank">P01889</a></td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, ALS, Stroke</td></tr>
<tr><th>Expression</th><td>All nucleated cells, microglia, immune cells</td></tr>
</table>
</div>

Overview

HLA-B (Major Histocompatibility Complex Class I B) is a gene located on chromosome 6p21.3 that encodes the 44 kDa heavy chain of the HLA class I molecule. HLA-B is one of the most polymorphic genes in the human genome, with over 6,000 known alleles[@klein2000]. It plays a critical role in adaptive immune surveillance by presenting endogenously synthesized peptide antigens to CD8+ cytotoxic T lymphocytes, enabling recognition and elimination of infected or abnormal cells[@shiina2009].

HLA molecules also interact with killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells, regulating NK cell activity through a sophisticated system of activating and inhibitory signals. This HLA-KIR interaction pathway has been implicated in neuroinflammatory processes relevant to [Alzheimer's disease](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease)[@hamzelou2021].

Molecular Function

Peptide Antigen Presentation

HLA-B folds around an 8-11 amino acid peptide derived from intracellular protein processing. The peptide-binding groove (alpha-1 and alpha-2 domains) contains polymorphic residues that determine which peptides can bind, shaping the repertoire of antigens presented to T-cells[@sidney2012]. Each HLA-B molecule presents approximately 10,000-20,000 different peptide species at the cell surface.

Interaction with CD8+ T-cells

The conserved alpha-3 domain of HLA-B interacts with the CD8 co-receptor on cytotoxic T lymphocytes, providing a co-stimulatory signal that enhances T-cell receptor (TCR) engagement. This HLA-B/CD8 interaction is critical for the activation and clonal expansion of virus-specific and tumor-reactive CD8+ T-cells.

Regulation of NK Cells

HLA-B interacts with KIR receptors on NK cells. Specific HLA-B alleles either activate or inhibit NK cell cytotoxicity through this pathway. In the brain, microglial expression of HLA-B and its interaction with NK cell KIRs may regulate neuroinflammatory responses[@hindorff2009].

Disease Associations

Alzheimer's Disease

HLA class II genes (including HLA-DRB1) have been associated with AD risk, but HLA-B associations are emerging. Microglial HLA-B expression increases in AD brains, reflecting an active immune response. The HLA-B/KIR interaction pathway may modulate microglial activation states, influencing amyloid clearance efficiency and neuroinflammatory burden[@hamzelou2021].

Parkinson's Disease

Specific HLA-B variants modify [Parkinson's disease](/diseases/parkinsons-disease) risk through modulation of the adaptive immune response in the brain. HLA-B alleles may influence autoimmune components of PD pathogenesis, particularly in cases with earlier onset. Microglial [HLA-B presentation](/entities/mhc) of neuronal antigens could trigger cytotoxic CD8+ T-cell responses targeting dopaminergic neurons. Several GWAS studies have identified the MHC region on chromosome 6p21 as a PD risk locus.

Multiple Sclerosis

HLA-B27:05 and HLA-B44:02 alleles are associated with MS susceptibility and disease course. HLA-B44:02 may be protective against MS onset, while HLA-B27:05 is linked to atypical MS presentations with prominent spinal cord involvement.

Amyotrophic Lateral Sclerosis (ALS)

HLA associations have been reported in ALS cohorts, suggesting immune-mediated mechanisms may contribute to motor neuron degeneration. The MHC region harboring HLA-B shows pleiotropic effects across neurodegenerative diseases.

Stroke and Cerebrovascular Disease

HLA-B alleles influence susceptibility to ischemic stroke, likely through immune-mediated mechanisms affecting vascular inflammation and atherogenesis[@neumannhaefelin2008].

Expression

HLA-B is constitutively expressed at high levels on all nucleated cells:

• Brain — primarily on microglia, low expression on neurons and astrocytes
• Immune cells — macrophages, dendritic cells, B-cells
• Endothelial cells — regulates immune surveillance at the blood-brain barrier

Common Variants

| Variant | Association | Effect |
|---------|-------------|--------|
| HLA-B*07:02 | Neutral | Common in European populations |
| HLA-B*27:05 | MS, ankylosing spondylitis | Autoimmune risk |
| HLA-B*44:02 | MS (protective) | Modulates disease risk |
| HLA-B*57:01 | HIV control | Enhanced viral peptide presentation |
| HLA-B*35:01 | Stroke risk | Altered immune response |

Therapeutic Implications

• HLA typing is critical for transplantation and predicting graft-versus-host disease
• HLA-B*57:01 testing is required before abacavir prescription to prevent hypersensitivity reactions
• Immunotherapy targets — HLA-B/peptide complexes are being explored as therapeutic targets in autoimmune diseases
• KIR-HLA blockade — therapeutic modulation of the KIR-HLA interaction may offer neuroprotective strategies in neurodegenerative disease

See Also

• [Major Histocompatibility Complex](/entities/mhc) — HLA system overview](/entities)
• [Microglia in Neuroinflammation](/cell-types/microglia-neuroinflammation) — immune cells expressing HLA-B in brain](/cell-types/microglia-neuroinflammation)
• [Alzheimer's Disease](/diseases/alzheimers-disease) — primary disease association
• [Parkinson's Disease](/diseases/parkinsons-disease) — primary disease association](/proteins/parkin)
• [Multiple Sclerosis](/diseases/multiple-sclerosis) — related autoimmune disorder

References