Dominance of a single peptide bound to the class I(B) molecule, Qa-1b.

Abstract

One of the hallmarks of class I(A) molecules is their ability to bind and present a wide array of peptides to CD8 T cells. This diversity is consistent with their ability to restrict a variety of pathogenic peptide epitopes as well as elicit strong transplantation responses. In contrast, class I(B) molecules appear to be involved in presentation of pathogenic epitopes to a relatively lesser extent as well as play a minor role in transplantation responses. Here we have examined the peptides bound and presented by the class I(B) molecule Qa-1b in order to determine if their diversity was similar to that reported for class I(A) Ags. First, we show that bulk-cultured anti-Qa-1b CTL predominantly recognize a single peptide (Qdm) derived from the leader segment of class I(A) alloantigens. These CTL are peptide specific and reflect the activity of previously described CTL clones. Second, we find approximately 4.6 x 10(4) copies of the Qdm peptide/cell. Most of the peptide is Qa-1b associated since the recovery of this peptide from anti-Qa-1b immunoprecipitates is approximately 75% of that seen in whole cell extracts and no detectable activity is observed in Kb or Db extracts from H-2b lymphoblasts. Third, the expression of Qa-1b on lymphoblasts is approximately 1 to 1.25 x 10(4) molecules/cell indicating that the Qdm peptide must be derived from both cell membrane and intracellular compartments. Finally, examination of the diversity of peptides associated with Qa-1b as determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry indicates few detectable peptide species associated with this molecule. Taken together, Qa-1b appears to predominantly bind a single peptide species that is recognized by alloreactive CD8 T cells. This feature may account, in part, for the class I(B) properties of this molecule.