Unlike the highly polymorphic class IA molecules, (H-2K,D,L) class IB molecules (Q,T,M) display little or no polymorphism, suggesting they may play a unique role in immune responses. There are 4-6 well defined alleles of the class IB molecule Qa-1, although data suggest that additional allcles may exist. Recently, two allo peptides were described which bind to Qa-lb and are recognized by CD8+ T cells. The Qdm+ (AMAPRTLLL) and Qdm (AMVPRTLU.) peptides are derived from leader sequences of H-2D molecules, but are dependent upon the Tap transporter for presentation by Qa-lb. Studies using recombinant inbred mice suggested that Qa-P also binds and presents Qdm. Using mutagenesis and four rounds of antibody (anti-H-2d) plus complement and anti-Qa-1a specific CTL depletions, we have generated a Tap-defective cell une from the NZB derived (H-2d, Qa-la)plasmacytoma PCI 1198. Similar to what is seen for Qa-1b on the Tap-defective line RMA-S, our Qa-1a cell line, PCK. 1, is not recognized by Qdm-peptide dependent anti-Qa-1b CTL unless pre-incubated with Qdm+ peptide. However, as was seen with Qa-1b, other anti-Qa-1a CTL recognize PCK. 1 in the presence or absence of Qdm-1a. Thus, despite differences in the peptide binding pockets of Qa-1a and Qa-1b ( V/l 24, H/T 9) both alleles of Qa-1 bind Qdm+ and are recognized on Tap-defective cells. The limited functional polymorphism and unusual peptide binding of Qa-1 may be of importance to the role Qa-1 plays in the immune response.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology