The Presentation of Self-Peptides: Tolerance and Competition

Abstract

Within the last 15 years, the pendulum of immune preoccupation has swung vigorously in the direction of the self. It is now commonplace to note that the T cell repertoire is acquired through a complex positive and negative selective process of recognition of self molecules in an MHC context. Accordingly, the repertoire “directed against foreign antigens” merely represents fortuitous cross-reactivity by the T cells selected by means of self-determinants.

The definition of “self” protein or self-T cell determinant is not an unambiguous one. The most inclusive definition would enumerate all overlapping sequences of 15 amino acids of all proteins coded for by the DNA of the organism including any mutants. A clearly more restrictive definition would only include those proteins that have access to the immune system and the major histocompatibility complex (MHC). Still more restrictive is the idea of a “dominant self” that includes only those determinants which are easily processed and presented, and which can bind with high affinity to one of the MHC Class I and Class II molecules. An interesting issue which also must be discussed is the concept of the “immune self” [1] which includes idiopeptides from both B cell receptor and T cell receptor variable regions, and MHC peptides, as well as other non-variable components derived from the immune system. In this paper, we will address some issues relating to the interactions of self-determinants with the MHC and the induction of tolerance.

Key Words:

• chimeric peptides
• dominant self
• immune self
• MHC peptides
• peptide competition
• tolerance