DOMINANCE OF A SINGLE PEPTIDE BOUND TO THE CLASS I-B MOLECULE, QA-1(B)

One of the hallmarks of class I-A molecules is their ability to bind a nd present a wide array of peptides to CD8 T cells. This diversity is consistent with their ability to restrict a variety of pathogenic pept ide epitopes as well as elicit Strong transplantation responses. In co ntrast, class I-B molecules appear to be involved in presentation of p athogenic epitopes to a relatively lesser extent as well as play a min or role in transplantation responses. Here we have examined the peptid es bound and presented by the class I-B molecule Qa-1(b) in order to d etermine if their diversity was similar to that reported for class I-A Ags. First, we show that bulk-cultured anti-Qa-1(b) CTL predominantly recognize a single peptide (Qdm) derived from the leader segment of c lass I-A alloantigens. These CTL are peptide specific and reflect the activity of previously described CTL clones. Second, we find approxima tely 4.6 x 10(4) copies of the Qdm peptide/cell. Most of the peptide i s Qa-1(b) associated since the recovery of this peptide from anti-Qa-1 (b) immunoprecipitates is similar to 75% of that seen in whole cell ex tracts and no detectable activity is observed in K-b or D-b extracts f rom H-2(b) lymphoblasts. Third, the expression of Qa-1(b) on lymphobla sts is similar to 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 assoc iated with Qa-1(b) as determined by matrix-assisted laser desorption/i onization time-of-flight mass spectrometry indicates few detectable pe ptide species associated with this molecule. Taken together, Qa-1(b) a ppears to predominantly bind a single peptide species that is recogniz ed by alloreactive CD8 T cells. This feature may account, in part, for the class I-B properties of this molecule.