       Document 0737
 DOCN  M9620737
 TI    High-density presentation of an immunodominant minimal peptide on B
       cells is MHC-linked to Th1-like immunity.
 DT    9602
 AU    Murray JS; Kasselman JP; Schountz T; Division of Biology, Kansas State
       University, Manhattan 66506,; USA.
 SO    Cell Immunol. 1995 Nov;166(1):9-15. Unique Identifier : AIDSLINE
       MED/96067650
 AB    Ligand-directed differences in the amount of peptide presented on a
       specific 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 density
       on the APC of Th1 responders (I-As genotypes) than on the APC of Th2
       responders (I-Ab genotypes). MHC-linked high peptide density is
       expressed on B lymphocytes, predominantly those that bear the B7-2
       activation marker/costimulatory ligand. We further investigated the role
       of I-As-specific polymorphism with transfected cells bearing an R-->Q
       change at position-70 of A beta (found only in the I-As allele).
       Strikingly, I-Ab-restricted Th1 and Th2 clones proliferate at a peptide
       dose 10- to 100-fold lower than wild-type on transfected fibroblasts
       bearing this single s-like substitution in A beta b. Moreover, the shift
       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 presented
       to a given TCR on activated B cells.
 DE    Amino Acid Sequence  Animal  *Antigen Presentation  Antigens,
       CD80/METABOLISM  B-Lymphocytes/*IMMUNOLOGY  Cell Separation
       Collagen/IMMUNOLOGY  Dose-Response Relationship, Immunologic  Female
       Haplotypes/IMMUNOLOGY  Histocompatibility Antigens Class II/*IMMUNOLOGY
       Immunodominant Epitopes/ANALYSIS/*IMMUNOLOGY  Lysine/IMMUNOLOGY  Male
       Mice  Mice, Inbred A  Mice, Inbred C57BL  Molecular Sequence Data
       Mutation/IMMUNOLOGY  Peptide Fragments/IMMUNOLOGY  Polymorphism
       (Genetics)/IMMUNOLOGY  Spleen/CYTOLOGY  Support, Non-U.S. Gov't  Th1
       Cells/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

