Creation of H-2 class I epitopes using synthetic peptides: Recognition by alloreactive cytotoxic T lymphocytes

Abstract

A major role that cytotoxic T lymphocytes (CTLs) play in the immune response is the specific destruction of viral-infected cells and tissue from foreign grafts. Class I molecules encoded within the major histocompatibility complex are the target structures for these CTLs. Recently, viral-restricted CTLs have been shown to recognize viral peptides in association with class I molecules, while several studies with cloned alloreactive CTLs have indicated that these T cells can recognize class I-derived peptides in association with class I molecules. Together, these observations suggest that peptide binding is an important function of class I molecules. In this paper, we show that the recognition of a particular class I molecule by a bulk population of alloreactive CTLs can be altered by incubating with it a peptide derived from another class I molecule. Specifically, we used the hybrid D/L(dm1 molecule as a target structure together with the peptide L(d)61-85, and we have shown that their associative recognition by L(d)-specific CTLs depends on sequence and configuration of the peptide and is specific for L(d) using a cold-target inhibition assay. Our results are discussed in light of three possible models for the target structure(s) that can be recognized by alloreactive CTLs and in terms of the role peptides may play during allorecognition.