TRA Gene

TRA (TRA= acronym for T Cell Receptor Alpha Locus) is a protein coding gene located on chromosome 14q11.2. The encoded protein forms the alpha chain of the complex alpha-beta T cell receptor.

Thus, the alpha chain of the alpha beta T cell receptor (TR) is specific for the immunodominant epitope GILGFVFTL of influenza A virus (IAV), which is restricted to HLA-A and contains M/matrix protein 1. It can recognize sporadic influenza A virus (IAV) variants by molecular mimicry and thus induce immunity against different influenza strains.

Antigen recognition leads to TR-CD3 accumulation on the cell surface and intracellular activation of LCK, which phosphorylates the ITAM motifs of CD3G, CD3D, CD3E, and CD247, allowing recruitment of ZAP70. ZAP70 in turn phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome.

The LAT signal osome propagates signaling branches to three major signaling pathways:

• the calcium signaling pathway
• the mitogen-activated protein kinase (MAPK) kinase signaling pathway
• the nuclear factor NF-kappa-B (NF-kB) signaling pathway

This activation cascade leads to the mobilization of transcription factors that are critical for gene expression and essential for the differentiation of T cells into effector/memory T cells.

Furthermore, the alpha-beta T cell receptor alpha chain recognizes tumor-specific or -associated metabolites essential for cancer cell survival and triggers killing of many cancer cell types,including lung, melanoma, leukemia, colon, breast, prostate, bone, and ovarian cancer cells.

1. Li SX et al. (2020) Identification of a t(X;17)(q28;q21) generating a KANSL1-MTCP1 gene fusion leading to dysregulated expression of MTCP1 in acute myeloid leukemia. Genes Chromosomes Cancer 59:417-421.

2. Ouyang H et al. (2019) Relationship between T-cell receptor α gene polymorphisms and symptomatic differences in patients with narcolepsy type 1. Chin Med J (Engl) 132:1796-1801.
3. Paria BC et al. (2021) Rapid Identification and Evaluation of Neoantigen-reactive T-Cell Receptors From Single Cells. J Immunother 44:1-8.