M1-specific T cell receptor alpha chain

Definition:

The alpha chain of TRAV27*01J42*01C*01/TRBV19*01J2S7*01C*02 alpha-beta T cell receptor (TR) clonotype that is specific for HLA-A*02:01-restricted M/matrix protein 1 immunodominant epitope GILGFVFTL of influenza A virus (IAV). Classified as a public TR clonotype, it is preferentially selected in effector memory CD8-positive T cells among multiple HLA-A*02:01 carriers and confers long-lived immunity against IAV infection. Can cross-recognize sporadically emerging IAV variants by molecular mimicry, inducing immunity toward different influenza strains. Antigen recognition initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell differentiation into effector/memory T cells (By similarity).

References:

[1]. Guillaume B E Stewart-Jones, et al. A structural basis for immunodominant human T cell receptor recognition. Nat Immunol. 2003 Jul;4(7):657-63. [Content Brief]

[2]. Jeffrey Ishizuka, et al. The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain. Immunity. 2008 Feb;28(2):171-82. [Content Brief]

[3]. Sophie A Valkenburg, et al. Molecular basis for universal HLA-A*0201-restricted CD8+ T-cell immunity against influenza viruses. Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4440-5. [Content Brief]

[4]. P J Lehner, et al. Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment. J Exp Med. 1995 Jan 1;181(1):79-91. [Content Brief]

[5]. P A Moss, et al. Extensive conservation of alpha and beta chains of the human T-cell antigen receptor recognizing HLA-A2 and influenza A matrix peptide. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8987-90. [Content Brief]

[6]. Sneha Sant, et al. Single-Cell Approach to Influenza-Specific CD8+ T Cell Receptor Repertoires Across Different Age Groups, Tissues, and Following Influenza Virus Infection. Front Immunol. 2018 Jun 27;9:1453. [Content Brief]

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