Target intelligence / Profile preview

HLA class I histocompatibility antigen, A-2 alpha chain (HLA-A2)

Target
HLA-A2
Molecular classification
MHC class I, Receptor, Antigen-presenting molecule
01

Overview

HLA-A2 is a specific serotype within the human leukocyte antigen (HLA)-A group, which belongs to the Major Histocompatibility Complex (MHC) class I molecules (UniProt P01892). It is one of the most prevalent HLA alleles in human populations, particularly among Caucasians, making it a cornerstone for the development of HLA-restricted immunotherapies (PubMed: 31434684). The primary biological function of HLA-A2 is to present short, intracellularly derived peptides—typically 8 to 10 amino acids in length—on the cell surface for surveillance by CD8+ cytotoxic T cells (NCBI Gene: 3105). In oncology, HLA-A2 is critical because it presents tumor-associated antigens, such as gp100 or MAGE-A4, which can be targeted by engineered T-cell receptors (TCRs) or bispecific T-cell engagers (StatPearls: MHC). Drugs like Tebentafusp are specifically designed to bind the HLA-A*02:01 complex, redirecting T cells to attack uveal melanoma cells (FDA: Kimmtrak). Because HLA-A2 is highly polymorphic, therapeutic success depends on precise patient genotyping and the avoidance of cross-reactivity with similar peptides presented on healthy tissues (PubMed: 29109433). Consequently, HLA-A2 serves as both a vital therapeutic scaffold and a mandatory biomarker for patient selection in modern precision TCR-based medicine.

Other names
HLA-A*02MHC class I antigen A*2Human leukocyte antigen A2Major histocompatibility complex, class I, A2
02

Mechanism of action

Presentation of specific intracellularly derived peptides to the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, enabling the immune system to recognize and eliminate infected or malignant cells.

03

Biological functions

Antigen presentationImmune responseT cell activationSelf-nonself recognition
04

Disease associations

CancerInfectionAutoimmune diseaseGraft-versus-host disease
05

Safety considerations

Off-target toxicity due to cross-reactivity with other HLA allelesCytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)On-target off-tumor toxicity if the presented peptide is found on healthy tissue
06

Interacting drugs

Tebentafusp

4 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypePeptide-HLA complex expression level

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