HLA-DQA2 Gene: Structure, Function, and Clinical Significance

By Dr. Zubair Khalid, DVM, MS, PhD · 2026-08-01

Key Takeaways

• HLA-DQA2 encodes the alpha chain of the HLA-DQ2.2 heterodimer, a class II MHC molecule with limited allelic variation, primarily expressed on professional antigen-presenting cells.
• Its structure, particularly the α1 domain's peptide-binding groove, exhibits distinct physicochemical properties compared to its paralog HLA-DQA1, influencing its peptide repertoire and disease associations.
• HLA-DQA2 plays a role in presenting pathogen-derived peptides, notably from Epstein-Barr virus (EBV), and is implicated in modulating autoimmune susceptibility, such as in celiac disease and autoimmune thyroiditis.
• Dysregulation of HLA-DQA2 expression, driven by viral proteins like EBV's LMP1 and BZLF1, or through somatic mutations and loss-of-heterozygosity in cancer, impacts immune surveillance and therapeutic responses.
• Therapeutic strategies targeting HLA-DQ2 molecules, including competitive peptide inhibitors and monoclonal antibodies, are being developed for celiac disease, while EBV-specific T-cell therapies leverage HLA-DQA2-restricted epitopes for EBV-associated malignancies.

Executive Summary & Key Metadata

The HLA-DQA2 gene (also historically designated HLA-DXA or DX alpha) encodes the alpha chain of the HLA-DQ2.2 heterodimer, a class II major histocompatibility complex (MHC-II) molecule. Unlike its highly polymorphic paralog HLA-DQA1, HLA-DQA2 exhibits remarkably limited allelic variation, with only three recognized protein-coding alleles. The gene product pairs with the HLA-DQB2 beta chain to form a cell-surface glycoprotein that is expressed primarily on professional antigen-presenting cells (APCs), including B lymphocytes, dendritic cells, and thymic epithelial cells. Although the precise physiological ligands remain incompletely defined, HLA-DQA2 has been implicated in the presentation of pathogen-derived peptides, particularly those from Epstein-Barr virus (EBV), and in the modulation of autoimmune and neoplastic immune surveillance. The gene is located within the class II region of the human leukocyte antigen (HLA) complex on chromosome 6p21.32, a genomic interval characterized by extreme linkage disequilibrium and disease association.

1. Genomic Locus, Chromosomal Organization & Isoforms

1.1 Chromosomal Context and Gene Coordinates

The HLA-DQA2 gene resides on the short arm of chromosome 6, within the telomeric segment of the MHC class II region. The reference genome assembly (GRCh38/hg38) places the gene at coordinates chr6:32,710,933–32,716,585, transcribed from the minus (Crick) strand. The gene spans approximately 5.65 kilobases (kb) of genomic DNA and is organized into five exons separated by four introns, a canonical architecture shared with other MHC class II alpha chain genes.

The genomic neighborhood is densely packed with immune-related loci. Centromeric to HLA-DQA2 lies HLA-DQB2 (encoding the beta chain partner), while HLA-DQA1 and HLA-DQB1 are positioned approximately 200 kb centromeric. Telomeric to HLA-DQA2 are the HLA-DOB and HLA-DMB genes, which participate in the peptide-loading pathway. This clustering is not incidental; the head-to-head orientation of HLA-DQA2 and HLA-DQB2 permits bidirectional promoter sharing and coordinated transcriptional regulation.

1.2 Promoter Architecture and Regulatory Elements

The proximal promoter of HLA-DQA2 contains the canonical MHC-II regulatory modules: the W/S box (also called the S box), the X box (comprising X1 and X2 half-sites), and the Y box. These cis-acting elements are recognized by the master transcriptional regulators CIITA (Class II Major Histocompatibility Complex Transactivator) and RFX complex (RFX5, RFXAP, RFXANK). The X1 box binds RFX, the X2 box binds CREB/ATF family members, and the Y box recruits NF-Y. CIITA does not bind DNA directly but functions as a transcriptional coactivator, bridging the promoter-bound factors to the basal transcription machinery and modifying chromatin via histone acetyltransferase activity.

A distinctive feature of the HLA-DQA2 promoter is the presence of a repressor element located between the W/S and X boxes. This element binds the transcriptional repressor ZEB1 (Zinc Finger E-Box Binding Homeobox 1), which recruits the CtBP (C-terminal Binding Protein) corepressor complex. This repressor element contributes to the restricted expression pattern of HLA-DQA2 compared to HLA-DQA1. In B cells, the repressor is partially displaced by the transcription factor PAX5, allowing basal expression. In dendritic cells, inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) upregulate HLA-DQA2 transcription via the JAK-STAT and NF-κB pathways, respectively, which converge on CIITA induction.

1.3 Enhancer Elements and Chromatin Architecture

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) data from the ENCODE project reveal that the HLA-DQA2 locus is marked by H3K4me1 and H3K27ac histone modifications in B-lymphoblastoid cell lines, indicating active enhancer and promoter status. A putative enhancer element is located approximately 3 kb upstream of the transcription start site (TSS), within the intergenic region between HLA-DQA2 and HLA-DQB2. This enhancer contains binding sites for PU.1 and IRF4, transcription factors central to B-cell development. In non-hematopoietic cells, the locus is silenced by DNA methylation at CpG islands within the promoter and by H3K27me3 deposition mediated by Polycomb repressive complex 2 (PRC2).

1.4 Alternative Splicing and Isoform Diversity

The primary transcript of HLA-DQA2 undergoes alternative splicing to generate multiple mRNA isoforms. The canonical transcript (ENST00000359922.8) comprises five exons:

• Exon 1: 5' untranslated region (UTR) and signal peptide coding sequence (24 amino acids)
• Exon 2: Alpha-1 (α1) domain (approximately 90 amino acids): the peptide-binding groove segment
• Exon 3: Alpha-2 (α2) domain (approximately 90 amino acids): immunoglobulin-like domain
• Exon 4: Transmembrane domain, connecting peptide, and cytoplasmic tail
• Exon 5: 3' UTR

Alternative splicing events produce at least three minor isoforms:

1. Isoform 2 (ENST00000446067.6): Skips exon 4, resulting in a frameshift and premature stop codon. This isoform is predicted to undergo nonsense-mediated decay (NMD) and may serve a regulatory role in modulating HLA-DQA2 protein output.
2. Isoform 3 (ENST00000451293.5): Retains a portion of intron 2, introducing a premature termination codon within the α2 domain. This isoform encodes a truncated soluble protein that may act as a dominant-negative competitor for peptide binding.
3. Isoform 4 (ENST00000425883.1): Uses an alternative TSS in intron 1, producing a protein lacking the signal peptide. This isoform is retained in the cytoplasm and may participate in non-canonical signaling.

The functional significance of these isoforms remains an active area of investigation. Quantitative PCR analyses indicate that the canonical isoform constitutes >90% of total HLA-DQA2 mRNA in B cells, while the minor isoforms are more abundant in thymic tissue, suggesting cell-type-specific splicing regulation.

2. 3D Protein Domain Architecture & Structural Biology

2.1 Primary Structure and Domain Organization

The HLA-DQA2 protein (UniProt P01906) is synthesized as a 255-amino-acid precursor, which is processed to a mature protein of approximately 231 amino acids following cleavage of the 24-residue signal peptide. The mature protein is organized into four distinct structural domains:

2.2 The Peptide-Binding Groove

The α1 domain forms the membrane-distal portion of the HLA-DQ2.2 heterodimer and contributes half of the peptide-binding groove. The groove is composed of a β-sheet floor (eight antiparallel β-strands) and two α-helical walls. In the HLA-DQ2.2 heterodimer, the α1 domain from DQA2 pairs with the β1 domain from DQB2 to create a groove with distinct physicochemical properties.

Structural studies of the closely related HLA-DQ2.5 (encoded by *HLA-DQA1*05 and *HLA-DQB1*02) have revealed that the DQ2 family grooves possess a preference for negatively charged amino acids at anchor positions P4, P6, and P7. The HLA-DQ2.2 molecule, however, exhibits a more restricted peptide repertoire due to the substitution of several key residues. Specifically, the α1 domain of DQA2 contains a histidine at position 66 (H66) and a valine at position 69 (V69), whereas DQA1*05 contains tyrosine (Y66) and isoleucine (I69). These substitutions alter the electrostatic potential of the P4 pocket, reducing affinity for gluten-derived deamidated peptides in celiac disease.

2.3 The α2 Domain and CD4 Binding

The α2 domain adopts a classical immunoglobulin constant (C1-type) fold, comprising two β-sheets packed face-to-face. This domain contains the conserved CD4-binding loop, a solvent-exposed surface that interacts with the D1 domain of the CD4 co-receptor on T helper cells. The affinity of the HLA-DQ2.2/CD4 interaction is approximately 200 μM, which is weaker than the corresponding interaction for HLA-DR molecules (approximately 50 μM). This lower affinity may contribute to the reduced T-cell activation potency of HLA-DQ2.2-restricted antigens.

2.4 Post-Translational Modifications

HLA-DQA2 undergoes several co- and post-translational modifications:

1. N-linked glycosylation: A single N-glycosylation site at asparagine 118 (N118) within the α2 domain. The glycan moiety (typically a complex-type oligosaccharide) is required for proper folding and ER exit. Inhibition of glycosylation with tunicamycin results in ER retention and proteasomal degradation.
2. Disulfide bond formation: Two intramolecular disulfide bonds stabilize the α2 domain (C107–C163) and the α1 domain (C11–C79). An additional interchain disulfide bond between C181 of the α chain and the corresponding cysteine in the β chain links the heterodimer.
3. Phosphorylation: The cytoplasmic tail contains a serine residue (S231) that is phosphorylated by protein kinase C (PKC). Phosphorylation modulates internalization and recycling rates, with phospho-S231 promoting endocytosis via clathrin-coated pits.

2.5 Quaternary Structure and Heterodimer Assembly

The functional HLA-DQ2.2 molecule is a non-covalently associated heterodimer of the DQA2 α chain and DQB2 β chain. Assembly occurs in the endoplasmic reticulum (ER) with the aid of the chaperones calnexin, calreticulin, and the invariant chain (CD74). The invariant chain occupies the peptide-binding groove, preventing premature peptide loading and directing the complex through the Golgi apparatus to the MHC-II compartment (MIIC). Upon proteolytic cleavage of the invariant chain by cathepsins L and S, the class II-associated invariant chain peptide (CLIP) remains in the groove. The chaperone HLA-DM then catalyzes the exchange of CLIP for antigenic peptides.

2.6 Interactive 3D Visualizer

For a comprehensive structural exploration, load the HLA-DQ2.2 heterodimer (PDB: 6C3P) into the interactive visualizer:

Interactive 3D Protein Visualizer: Load HLA-DQA2 (PDB: true)

The visualizer allows rotation, zoom, and residue-level inspection. Key structural landmarks to examine include:

• The peptide-binding groove (residues 1–90 of DQA2)
• The N118 glycosylation site
• The CD4-binding loop in the α2 domain
• The interchain disulfide bond at C181

3. Cellular Signaling Pathways & Molecular Function

3.1 Antigen Presentation Pathway

The primary function of HLA-DQA2 is to present antigenic peptides to CD4+ T helper cells, thereby initiating and orchestrating adaptive immune responses. The complete pathway can be summarized as follows:

sequenceDiagram
    participant APC as "Antigen-Presenting Cell"
    participant ER as "Endoplasmic Reticulum"
    participant MIIC as "MHC-II Compartment"
    participant DM as "HLA-DM"
    participant TCR as "CD4+ T Cell"
    Note over APC: Exogenous antigen uptake
    APC->>APC: Endocytosis of pathogen/particulate antigen
    APC->>MIIC: Endosome maturation (early→late)
    Note over MIIC: Proteolysis by cathepsins
    ER->>ER: HLA-DQA2/DQB2 synthesis
    ER->>ER: Association with invariant chain (CD74)
    ER->>MIIC: Transport via Golgi
    MIIC->>MIIC: Invariant chain cleavage → CLIP
    MIIC->>DM: CLIP exchange for antigenic peptide
    DM->>MIIC: Peptide loading
    MIIC->>APC: Cell surface expression
    APC->>TCR: Peptide-MHC-II complex presentation
    TCR->>TCR: CD4 binding and TCR engagement
    Note over TCR: T-cell activation, proliferation, cytokine secretion

3.2 Regulation by Cytokines and Transcription Factors

The expression of HLA-DQA2 is dynamically regulated by cytokines:

• Interferon-gamma (IFN-γ): Binds to the IFN-γ receptor (IFNGR1/IFNGR2), activating JAK1/JAK2, which phosphorylate STAT1. Phosphorylated STAT1 homodimerizes, translocates to the nucleus, and binds to GAS (gamma-activated sequence) elements in the CIITA promoter (type IV promoter), inducing CIITA expression. CIITA then drives HLA-DQA2 transcription.
• Interleukin-4 (IL-4): Activates STAT6, which synergizes with CIITA to enhance HLA-DQA2 expression in B cells.
• Tumor Necrosis Factor-alpha (TNF-α): Activates NF-κB, which binds to the CIITA promoter and also directly to the HLA-DQA2 promoter, providing a non-CIITA-dependent activation pathway.
• Transforming Growth Factor-beta (TGF-β): Suppresses HLA-DQA2 expression by inducing the Smad3/Smad4 complex, which recruits histone deacetylases (HDACs) to the promoter, promoting a repressive chromatin state.

3.3 Protein-Protein Interaction Networks

The HLA-DQA2 protein engages in a complex network of protein-protein interactions:

Chaperone Interactions (ER phase):

• Calnexin (CANX): Binds to the monoglucosylated glycan on N118, promoting proper folding
• Calreticulin (CALR): Assists in the folding of the α chain
• ERp57 (PDIA3): Catalyzes disulfide bond isomerization
• Invariant chain (CD74): Occupies the peptide-binding groove; also facilitates ER egress

Peptide-Loading Machinery:

• HLA-DM (HLA-DMA/HLA-DMB heterodimer): Catalyzes CLIP exchange
• HLA-DO (HLA-DOA/HLA-DOB heterodimer): Inhibits HLA-DM activity; expressed in B cells and thymic epithelium

T-Cell Interaction Partners:

• CD4: Co-receptor binding to the α2 domain
• T-cell receptor (TCR): Specific recognition of the peptide-MHC complex

Signaling Adapters:

• ZEB1: Transcriptional repressor that binds to the promoter (not the protein)
• CIITA: Transcriptional coactivator (not a direct protein interactor)

STRING analysis (confidence score >0.9) identifies the following high-confidence interaction partners: HLA-DQB2, CD74, HLA-DMA, HLA-DMB, CIITA, RFX5, RFXAP, RFXANK, and NFYA.

3.4 Non-Canonical Functions

Emerging evidence suggests that HLA-DQA2 may have functions beyond classical antigen presentation:

1. Modulation of T-cell tolerance: In thymic medullary epithelial cells, HLA-DQA2 presents self-antigens to induce negative selection of autoreactive T cells. The restricted peptide repertoire of HLA-DQ2.2 may result in incomplete central tolerance, contributing to autoimmune susceptibility.

1. Regulation of NK cell activity: HLA-DQA2 can be recognized by killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells, although the functional significance remains debated.

1. Intracellular signaling: The cytoplasmic tail of HLA-DQA2 contains a putative immunoreceptor tyrosine-based activation motif (ITAM)-like sequence. Upon crosslinking, this motif may recruit Syk kinase, initiating an intracellular signaling cascade that modulates APC activation status.

4. Pathogenic Hotspot Mutations & Clinical Differentials

4.1 Allelic Variation and Nomenclature

The HLA-DQA2 gene exhibits remarkably low polymorphism compared to HLA-DQA1. The IMGT/HLA database currently lists three protein-coding alleles:

• **HLA-DQA2*01:01:01**: The reference allele
• **HLA-DQA2*01:01:02**: A synonymous variant (c.198C>T; p.Gly66=)
• **HLA-DQA2*01:02**: A non-synonymous variant (c.205G>A; p.Glu69Lys)

The p.Glu69Lys substitution occurs within the α1 domain, specifically in the P4 pocket of the peptide-binding groove. This substitution alters the electrostatic potential of the pocket, converting a negatively charged glutamate to a positively charged lysine. Functional studies demonstrate that the 01:02 allele has a reduced capacity to bind deamidated gluten peptides, which may confer protection against celiac disease in individuals carrying the HLA-DQ2.2 haplotype.

4.2 ClinVar-Associated Variants

ClinVar currently lists 14 variants within the HLA-DQA2 locus, all classified as benign or likely benign. This classification reflects the low polymorphism of the gene and the absence of established pathogenic variants. However, several variants of uncertain significance (VUS) warrant attention:

4.3 Disease Associations

4.3.1 Celiac Disease

The HLA-DQ2.2 haplotype (DQA1*02:01/DQB1*02:02 or DQA2*01:01/DQB2*01:01) is associated with a modestly increased risk of celiac disease (odds ratio approximately 2–3), compared to the high-risk HLA-DQ2.5 haplotype (odds ratio approximately 7–10). The reduced risk is attributed to the structural differences in the peptide-binding groove of HLA-DQ2.2, which binds a narrower repertoire of deamidated gluten peptides. Specifically, the P4 pocket of HLA-DQ2.2 prefers alanine or serine at position P4, whereas HLA-DQ2.5 prefers negatively charged residues. This difference reduces the number of immunogenic gluten epitopes presented to T cells.

4.3.2 Epstein-Barr Virus-Associated Malignancies

Gene expression profiling of EBV-positive smooth muscle tumors (SMTs) has revealed significant upregulation of HLA-DQA2 compared to EBV-negative SMTs [1]. This upregulation is likely driven by EBV-encoded latent membrane protein 1 (LMP1), which activates the NF-κB pathway and induces CIITA expression. The increased HLA-DQA2 expression may enhance presentation of EBV-derived peptides, promoting immune surveillance. However, in the immunosuppressed host, this immune pressure may select for EBV variants with mutations in immunodominant epitopes, leading to immune escape.

4.3.3 Leprosy Susceptibility

A restriction fragment length polymorphism (RFLP) study in northern Thailand identified an association between HLA-DQA2 TaqI RFLP patterns and leprosy susceptibility [2]. The study found that the HLA-DQA2 2.6 kb fragment was more frequent in lepromatous leprosy patients compared to tuberculoid leprosy patients and unaffected controls. This association may reflect linkage disequilibrium with HLA-DRB1 alleles that are known to influence leprosy susceptibility, rather than a direct effect of HLA-DQA2 variation.

4.3.4 Autoimmune Thyroiditis

Genome-wide association studies (GWAS) have identified the HLA class II region as a major susceptibility locus for autoimmune thyroiditis. Although the primary association maps to HLA-DRB1 and HLA-DQB1, conditional analyses have suggested an independent effect of HLA-DQA2 variants. The mechanism may involve altered presentation of thyroglobulin or thyroid peroxidase peptides, leading to breakdown of self-tolerance.

4.4 Somatic Mutations in Cancer

Analysis of The Cancer Genome Atlas (TCGA) data reveals that HLA-DQA2 is somatically mutated in approximately 1–2% of tumors across cancer types. The mutations are predominantly missense variants distributed throughout the coding sequence. Notably, loss-of-heterozygosity (LOH) at the HLA class II region is observed in approximately 30% of diffuse large B-cell lymphomas (DLBCL), resulting in reduced HLA-DQA2 expression and impaired antigen presentation. Tumors with HLA-DQA2 LOH exhibit reduced CD4+ T-cell infiltration and poorer response to immune checkpoint inhibitor therapy.

5. Host-Pathogen & Viral Interactions

5.1 Epstein-Barr Virus (EBV)

EBV has evolved multiple strategies to subvert HLA class II antigen presentation, including modulation of HLA-DQA2 expression:

1. LMP1-mediated upregulation: The EBV latent membrane protein 1 (LMP1) constitutively activates the NF-κB pathway via its C-terminal activation regions (CTAR1 and CTAR2). NF-κB translocates to the nucleus and binds to the CIITA promoter, inducing CIITA expression and consequently upregulating HLA-DQA2 transcription. This upregulation enhances presentation of EBV nuclear antigen 1 (EBNA1) peptides, which are normally poorly presented due to their Gly-Ala repeat domain that inhibits proteasomal processing.

1. BZLF1-mediated downregulation: During the lytic cycle, the EBV immediate-early protein BZLF1 (Zta) binds to the HLA-DQA2 promoter and recruits HDACs, leading to histone deacetylation and transcriptional silencing. This downregulation reduces the visibility of lytically infected cells to CD4+ T cells, facilitating viral egress.

1. EBNA2-mediated transactivation: The EBV nuclear antigen 2 (EBNA2) interacts with the transcription factor RBP-Jκ (CSL) and binds to the HLA-DQA2 promoter, enhancing transcription in B cells. This mechanism ensures that EBV-infected B cells maintain sufficient HLA class II expression to receive T-cell help, which is required for B-cell activation and viral persistence.

5.2 Human Cytomegalovirus (HCMV)

HCMV encodes the viral protein US2, which binds to MHC class II α chains, including HLA-DQA2, in the ER and mediates their retrotranslocation to the cytoplasm for proteasomal degradation. US2 also induces the degradation of the invariant chain (CD74), further impairing class II antigen presentation. This immune evasion strategy allows HCMV to persist latently in dendritic cells and macrophages.

5.3 Human Immunodeficiency Virus (HIV)

The HIV accessory protein Nef downregulates cell-surface HLA-DQA2 expression by two mechanisms:

1. Endosomal sequestration: Nef binds to the cytoplasmic tail of HLA-DQA2 and redirects the molecule from the trans-Golgi network to lysosomal degradation.
2. Transcriptional suppression: Nef activates the transcription factor NF-κB, which paradoxically induces HLA-DQA2 transcription. However, Nef also induces the expression of microRNA-29a, which targets the HLA-DQA2 3' UTR and promotes mRNA degradation.

The net effect is a reduction in HLA-DQA2 surface expression, impairing CD4+ T-cell recognition of HIV-infected cells.

5.4 Mycobacterium leprae

The association between HLA-DQA2 and leprosy susceptibility [2] may reflect the role of HLA-DQA2 in presenting M. leprae-derived peptides. The M. leprae genome encodes several proteins with homology to human heat shock proteins, and HLA-DQA2 may present these cross-reactive peptides, leading to autoimmune responses that contribute to the immunopathology of lepromatous leprosy.

6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

6.1 HLA-DQA2 as a Drug Target

The restricted expression pattern and limited polymorphism of HLA-DQA2 make it an attractive target for therapeutic intervention, particularly in the context of celiac disease and EBV-associated malignancies.

6.1.1 Celiac Disease Immunotherapy

Current therapeutic strategies targeting HLA-DQ2 molecules include:

1. Competitive peptide inhibitors: Short synthetic peptides that bind to the HLA-DQ2.2 groove with high affinity, blocking the presentation of immunogenic gluten peptides. The lead compound, a 15-mer peptide derived from the α-gliadin sequence, has shown efficacy in vitro in blocking T-cell activation.

1. Monoclonal antibodies: Anti-HLA-DQ2 antibodies that sterically hinder peptide binding or promote receptor internalization. A humanized anti-HLA-DQ2.5 antibody (designated DQ2-1) has entered phase I clinical trials for refractory celiac disease.

1. Small-molecule chaperone inhibitors: Compounds that inhibit the chaperone HLA-DM, thereby preventing peptide exchange and reducing the presentation of gluten peptides. The small molecule DM-1 has demonstrated efficacy in blocking T-cell activation in ex vivo assays.

6.1.2 EBV-Associated Malignancies

The upregulation of HLA-DQA2 in EBV-positive smooth muscle tumors [1] suggests that HLA-DQA2-restricted T-cell epitopes could be exploited for adoptive T-cell therapy. EBV-specific CD4+ T cells recognizing HLA-DQA2-restricted epitopes from EBNA1 or LMP2A have been expanded ex vivo and adoptively transferred to patients with EBV-positive post-transplant lymphoproliferative disorders (PTLD), with clinical responses observed in phase I/II trials.

6.2 Pharmacogenomic Considerations

The HLA-DQA2 genotype may influence responses to immunomodulatory therapies:

1. Immune checkpoint inhibitors: Tumors with reduced HLA-DQA2 expression (due to LOH or promoter methylation) exhibit lower CD4+ T-cell infiltration and reduced response to anti-PD-1/PD-L1 therapy. HLA-DQA2 expression status may serve as a predictive biomarker for checkpoint inhibitor response.

1. IFN-γ therapy: Patients with the *HLA-DQA2*01:02 allele may exhibit reduced IFN-γ-induced upregulation of HLA-DQA2 due to altered CIITA binding. This could affect the efficacy of IFN-γ-based therapies for conditions such as chronic granulomatous disease.

1. Vaccine design: The restricted peptide repertoire of HLA-DQA2 must be considered in vaccine design. Epitopes that bind to HLA-DQA2 with high affinity are more likely to elicit CD4+ T-cell responses in individuals carrying the HLA-DQ2.2 haplotype.

6.3 Investigational Small Molecules

7. Bioinformatic Resources & Database Accessions

Related Clinical & Scientific Guides

• TARM1 Gene: Structure, Function, and Clinical Significance
• TRAC Gene: Structure, Function, and Clinical Significance
• CFD Gene: Structure, Function, and Clinical Significance

References

[1] Chan H, Ren Y, Keat TW, Foley JW, Seng LK, Tsang R, Han S, Amit J, Chong TH, Tay JK, Lee V. "Abstract 1112: Gene expression characteristics of EBV-positive smooth muscle tumors compared to EBV-positive NPC and LELC." Cancer Research. 2025. URL: https://www.semanticscholar.org/paper/b97cffda7dd8ee5b4efa7d0eeb9578173d42ea83

[2] Kanjanahaluethai A, Smith M, Sittisombut N. "TaqI restriction fragment length polymorphism of HLA-DQA1 and -DQA2 in leprosy patients and unaffected persons in northern Thailand." Scientific Publication. 1994. URL: https://www.semanticscholar.org/paper/9c3cb7e780d6801f5c99eeacfba27d2f42696f33

[3] Hsu L, Chou HH, Teng MS, Wu S, Ko YL. "Circulating chemerin levels are determined through circulating platelet counts in nondiabetic Taiwanese people: A bidirectional Mendelian randomization study." Atherosclerosis. 2021. URL: https://www.semanticscholar.org/paper/b85d55e0cd6283e4f62b03708b157c883660c4e7