Clonal Deletion Prunes but Does Not Eliminate Self-Specific αβ CD8(+) T Lymphocytes

Area of Science:

• Immunology
• T cell biology
• Self-tolerance

Background:

• Clonal deletion is believed to efficiently eliminate self-reactive T cells from the peripheral immune system.
• The presence and function of self-specific T cells in healthy individuals remain incompletely understood.

Purpose of the Study:

• To investigate the frequency and functional state of self-peptide MHC-specific CD8(+) T cells in healthy humans.
• To determine if clonal deletion completely removes self-specific T cells or if a functional repertoire remains.

Main Methods:

• Quantification of self-peptide MHC-specific CD8(+) T cells in peripheral blood.
• Assessment of T cell anergy and responsiveness to peptide activation.
• Analysis of T cell repertoire diversity against viral epitopes.

Main Results:

• Self-peptide MHC-specific CD8(+) T cells are present at frequencies comparable to non-self-specific T cells.
• T cells specific for the SMCY antigen (Y chromosome-encoded) were found in both males and females, with only a modest frequency difference.
• These self-specific T cells exhibited anergy but could be activated by strong stimuli.
• T cells recognizing all variants of a hepatitis C virus epitope were detected, indicating broad repertoire coverage.

Conclusions:

• Clonal deletion partially removes, but does not eliminate, self-specific T cells.
• Maintaining a diverse T cell repertoire, including some self-reactive cells, may be crucial for defending against a wide range of pathogens.
• Complete elimination of self-specific T cells could create vulnerabilities in the immune system exploitable by pathogens.