Tissue distribution of natural peptides derived from a ubiquitous dehydrogenase, including a novel liver-specific peptide that demonstrates the pronounced specificity of low affinity T cell reactions

Abstract

The peptides recognized by CD8+ CTL normally arise by proteolysis of intracellular proteins. To learn whether these peptides are generated similarly in diverse cell types, we examined the variety and abundance of naturally processed peptides that derive from a ubiquitous enzyme, alpha-ketoglutarate dehydrogenase, and are recognized in association with the class I MHC protein, Ld, by a CTL clone (2C). A characteristic set of three peptides was found in diverse tissues, but their abundance varied greatly, apparently unrelated to differences in class I MHC expression, e.g., they were surprisingly abundant in liver. We also found in liver a fourth naturally processed peptide (p2Ca-Y4, LSPYPFDL) that differs by one oxygen atom from a previously characterized natural peptide (p2Ca, LSPFPFDL). CTL discrimination between these peptides in association with the same class I MHC protein, Kb, demonstrates the striking specificity that can be exhibited by low affinity T cell reactions.