The self-directed T cell repertoire: its creation and activation

Area of Science:

• Immunology
• Autoimmunity
• Cancer Immunology

Background:

• The self-directed T cell repertoire is vast and includes self-reactive T cells.
• These self-reactive T cells play a role in autoimmune diseases when self-antigens are presented.
• The composition of the residual self-reactive T cell repertoire is heterogeneous.

Purpose of the Study:

• To review the engagement of the self-reactive T cell repertoire.
• To elucidate the rules governing the stimulation of self-reactive T cells.
• To explore the dual role of self-reactive T cells in autoimmunity and cancer immunotherapy.

Main Methods:

• Review of existing literature on T cell repertoire, autoimmunity, and cancer immunology.
• Analysis of mechanisms underlying T cell activation against self-antigens.
• Discussion of therapeutic strategies targeting the self-reactive T cell repertoire.

Main Results:

• The self-reactive T cell repertoire comprises high and low affinity T cells against dominant, cryptic, and inflammation-presented determinants.
• Upregulation of cryptic self-determinants can trigger autoreactivity and autoimmunity.
• The same T cell repertoires involved in autoimmunity can be therapeutically exploited for anti-cancer immunity.

Conclusions:

• Self-reactive T cells, particularly those against cryptic determinants, are implicated in both autoimmune diseases and cancer.
• Understanding the rules of self-reactive T cell engagement is crucial for developing therapies.
• Targeting cryptic tumor antigens offers a promising strategy for anti-cancer immunotherapy.