alpha-beta T cell lineage commitment

Definition

Target type: biologicalprocess

The process in which a pro-T cell becomes committed to becoming an alpha-beta T cell. [GOC:add, ISBN:0781735149]

Alpha-beta T cell lineage commitment is a complex process that involves the sequential expression of specific transcription factors and signaling pathways. The process begins with the differentiation of hematopoietic stem cells (HSCs) into multipotent progenitors (MPPs), which then commit to the lymphoid lineage. These lymphoid progenitors express the transcription factor GATA-3, which is essential for the development of both T and B cells.

As lymphoid progenitors progress further, they encounter Notch signaling, a critical pathway for T cell commitment. Notch signaling induces the expression of the transcription factor GATA-3 and other key T cell transcription factors, including TCF-1, LEF-1, and c-MYB. These factors suppress B cell lineage commitment and promote T cell fate.

The next stage involves the commitment to the alpha-beta lineage, where the cells acquire the ability to express the TCRαβ. This stage is characterized by the expression of the transcription factor Notch1, which promotes the expression of RAG1 and RAG2, essential for the rearrangement of the TCRα and TCRβ genes. The expression of CD4 and CD8 coreceptors also starts during this stage.

The process of alpha-beta T cell lineage commitment is tightly regulated and involves a complex interplay of signaling pathways, transcription factors, and cell-cell interactions. These interactions ensure that the proper selection of TCRαβ chains occurs and that T cells develop into functional effector cells capable of recognizing and responding to foreign antigens.

The final stage involves the selection of T cells based on the specificity of their TCRαβ. Cells that bind to self-antigens are eliminated through negative selection, while those that bind to foreign antigens with moderate affinity are positively selected and allowed to mature. This process ensures that the immune system targets only foreign antigens while avoiding the destruction of self-tissues.'
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