A viral peptide can mimic an endogenous peptide for allorecognition of a major histocompatibility complex class I product.

Alloreactive class I-restricted T cells may recognize the class I structure alone, in association with a specific peptide, or with any stabilizing peptide. We have tested the role of endogenous peptides in the recognition of H-2Kb molecules by two alloreactive cytolytic T lymphocyte (CTL) clones using the mutant tumor line RMA-S, which expresses its surface H-2b molecules devoid of peptides and is not lysed by these two CTL clones. Empty H-2b molecules on RMA-S cells can be stabilized by binding exogenously added peptides. H-2Kb-specific recognition of the RMA-S cells by one of the CTL clones was restored by endogenous peptide extracts which only minimally stabilized H-2Kb on the surface of RMA-S cells, indicating the requirement for a specific peptide on a limited number of H-2Kb molecules. In addition, one out of three peptides which greatly enhance the expression of H-2Kb, the nucleoprotein peptide 52-59 from vesicular stomatitis virus (VSV), was also able to restore the lysis of RMA-S cells by the clone. The recognition of a common motif by an alloreactive clone (H-2k anti-H-2Kb) and virus-specific Kb-restricted clones suggests that both H-2k and H-2b thymic environments allow selection of T cells capable of recognizing H-2Kb+VSV and that tolerance to self, as would be the case in the (H-2k x H-2b)F1 mice, would partially delete the repertoire of antiviral T cells.