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Selective events in T cell development

E Robey¹, B J Fowlkes

¹Department of Molecular and Cell Biology, University of California at Berkeley 94720.

Annual Review of Immunology

|January 1, 1994

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Mammalian immune cells undergo thymic selection to eliminate self-reactive T cells and ensure proper function. This process refines T cell receptors (TCRs) for effective foreign antigen recognition while preventing autoimmunity.

Area of Science:

Immunology
Molecular Biology
Developmental Biology

Background:

Somatic rearrangement of antigen receptor genes enables the immune system to recognize diverse foreign proteins.
This process can inadvertently produce self-reactive or nonfunctional T cell receptors (TCRs).
Thymic development involves rigorous T cell selection to eliminate potentially harmful or useless TCRs.

Purpose of the Study:

To elucidate the intricate mechanisms of T cell selection during thymic development.
To understand the interplay between T cell receptor gene rearrangement and selection processes.
To investigate how T cells are simultaneously selected for foreign peptide recognition and lineage commitment.

Main Methods:

Analysis of T cell development and selection checkpoints in the thymus.

Related Experiment Videos

Investigation of gene rearrangement processes, including beta gene rearrangement and allelic exclusion.

Examination of positive and negative selection mechanisms involving self-MHC and foreign peptide recognition.

Main Results:

T cell selection begins before antigen receptor gene rearrangement is complete, with a checkpoint for beta gene rearrangement.
This checkpoint is linked to rearrangement regulation and allelic exclusion, ensuring single TCR expression per cell.
Post-rearrangement, T cells undergo negative selection against self-reactivity and positive selection for recognition of foreign peptides bound to self-MHC molecules.

Conclusions:

Thymic T cell selection is a multi-stage process crucial for immune tolerance and effective adaptive immunity.
The coordination of gene rearrangement, checkpoints, and selection events ensures the generation of a functional T cell repertoire.
Positive selection also dictates the differentiation into CD4 helper or CD8 cytotoxic T cell lineages, a process still under investigation.