HIGH-DENSITY PRESENTATION OF AN IMMUNODOMINANT MINIMAL PEPTIDE ON B-CELLS IS MHC-LINKED TO TH1-LIKE IMMUNITY

Ligand-directed differences in the amount of peptide presented on a sp ecific APC subset could influence the functional outcome of any given immune response, We have investigated this issue with a biochemically determined immunodominant peptide that is presented at a higher densit y on the APC of Th1 responders (I-A(s) genotypes) than on the APC of T h2 responders (I-Ab genotypes), MHC-linked high peptide density is exp ressed on B lymphocytes, predominantly those that bear the B7-2 activa tion marker/costimulatory ligand. We further investigated the role of I-A(s)-specific polymorphism with transfected cells bearing an R-->Q c hange at position-70 of A beta (found only in the I-A(s) allele), Stri kingly, I-A(b)-restricted Th1 and Th2 clones proliferate at a peptide dose 10- to 100-fold lower than wild-type on transfected fibroblasts b earing this single s-like substitution in A beta(b), Moreover, the shi ft in the clone dose response is sensitive to the peptide's C-terminus , as is MHC-linked Th1-like immunity to this peptide in vivo. Together , these data suggest that ligand-density can dictate Th1/Th2 selection via a single MHC polymorphism that determines the level of peptide pr esented to a given TCR on activated B cells. (C) 1995 Academic Press, Inc.