Target intelligence / Profile preview

HLA-A*02:01 presenting the HA-2 minor histocompatibility antigen (HLA-A*02:01/HA-2)

Target
HLA-A*02:01/HA-2
Molecular classification
MHC class I, Peptide-MHC complex, Antigen
01

Overview

The HLA-A*02:01 presenting the HA-2 (UTA2-1) epitope is a peptide-major histocompatibility complex (pMHC) that serves as a highly specific target for immunotherapy in hematological malignancies. The HA-2 antigen is a minor histocompatibility antigen (mHAg) derived from the MYO1G gene (formerly known as UTA2-1), which is a member of the class I myosin family [1][2]. This epitope is presented specifically by the HLA-A*02:01 allele and is characterized by its restricted expression to cells of the hematopoietic lineage, including dendritic cells, monocytes, and leukemic cells [3]. Because of this tissue-restricted expression, the HLA-A*02:01/HA-2 complex is a prime candidate for TCR-based therapies designed to induce a graft-versus-leukemia (GVL) effect while minimizing the risk of systemic graft-versus-host disease (GVHD) [4]. Current therapeutic approaches involve the development of T-cell receptor (TCR) engineered T-cells that can recognize and eliminate HA-2-positive leukemic cells in patients who have undergone allogeneic stem cell transplantation [5].

Other names
HLA-A*02:01/MYO1GHA-2/UTA2-1 epitopeMinor histocompatibility antigen HA-2YIGEVLVSV peptide/HLA-A*02:01 complex
02

Mechanism of action

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte (CTL) activation and lysis of the target cell.

03

Biological functions

Antigen presentationT-cell activationImmune response
04

Disease associations

LeukemiaHematological malignancyGraft-versus-host disease
05

Safety considerations

Hematopoietic toxicityGraft-versus-host disease (GvHD)On-target off-tumor toxicity to healthy blood cells
06

Interacting drugs

HA-2-specific TCR-engineered T-cells
07

Biomarkers

HLA-A*02:01 positivityMYO1G expressionHA-2 peptide presentation

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