T cell immunity or tolerance as a consequence of self antigen presentation

Area of Science:

• Immunology
• Protein Biochemistry

Background:

• The fifth component of complement (C5) is a serum protein.
• C5-deficient mice lack C5 and do not develop tolerance to it.

Purpose of the Study:

• To investigate the mechanisms underlying immunity versus tolerance to mouse C5.
• To understand how self-antigens are presented to T cells to induce tolerance.

Main Methods:

• Immunization of C5-deficient mice with C5-sufficient serum.
• Analysis of CD4+ T cell responses.
• Assessment of C5 processing and presentation by antigen-presenting cells (APCs) from tolerant mice.
• Characterization of T cell recognition of C5 peptide/class II complexes.

Main Results:

• Immunization of C5-deficient mice induced CD4+ T cells recognizing C5 in a class II-restricted manner.
• T cells from C5-sufficient (tolerant) mice showed no C5-specific responses.
• Tolerant mice APCs processed and presented C5 via class II molecules, recognized by specific T cell clones.
• Antigen-presenting cells from C5-sufficient mice stimulated T cells using pre-formed C5 peptide/class II complexes generated in vivo.

Conclusions:

• Self-antigen presentation via class II molecules is crucial for inducing and maintaining T cell tolerance.
• In vivo generated C5 peptide/class II complexes are recognized by T cells in tolerant mice.
• The study elucidates a key mechanism of self-tolerance to serum proteins.