       Document 0294
 DOCN  M9650294
 TI    A mAb against HLA-A2 can be influenced both positively and negatively by
       the associated peptide.
 DT    9605
 AU    Barouch D; Davenport M; McMichael A; Reay P; Nuffield Department of
       Clinical Medicine, Institute of Molecular; Medicine, John Radcliffe
       Hospital, Oxford, UK.
 SO    Int Immunol. 1995 Oct;7(10):1599-605. Unique Identifier : AIDSLINE
       MED/96128653
 AB    Presentation of peptides by class I HLA molecules is essential for the
       development of a T cell-mediated immune response. TCRs have the ability
       to discriminate among large numbers of different HLA-peptide complexes.
       We have identified a mAb, MA2.1, that also discriminates among HLA-A2
       associated with different peptides. A soluble form of HLA-A2 bound to
       single peptides was prepared and its serological reactivity was studied
       using four mAbs. Three antibodies, W6/32, BB7.2 and BBM.1, recognized
       all the complexes equally. MA2.1, however, recognized most of the
       complexes equally but showed markedly different reactivity to two
       peptides bound to HLA-A2. MA2.1 recognized HLA-A2 complexed with the
       HIV-1 p17 epitope (SLYNTVATL) at least 30 times more strongly than all
       other complexes studied and this enhanced reactivity was found to be
       sensitive to a point mutation of threonine to alanine at position 8 in
       the peptide. In addition, MA2.1 had a very low reactivity for HLA-A2
       complexed with the peptide TLWVDPYEV. Previous studies have mapped the
       binding epitope of MA2.1 to the alpha 1 and alpha 2 helices of HLA-A2,
       suggesting two possible explanations for the ability of the bound
       peptide to influence MA2.1 reactivity. Either MA2.1 is sensitive to
       peptide-induced conformational changes of the helices, or it directly
       contacts certain peptides in the groove of HLA-A2.
 DE    Amino Acid Sequence  Animal  Antibodies, Monoclonal/*IMMUNOLOGY
       Antibody Specificity  *Antigen Presentation  Comparative Study
       Epitopes/GENETICS/IMMUNOLOGY  Gene Products, gag/GENETICS/IMMUNOLOGY
       Herpesvirus 4, Human/IMMUNOLOGY  Human  HIV Antigens/GENETICS/IMMUNOLOGY
       HIV-1/GENETICS/IMMUNOLOGY  HLA-A2 Antigen/*IMMUNOLOGY  Macromolecular
       Systems  Mice  Models, Molecular  Molecular Sequence Data  Peptide
       Fragments/*IMMUNOLOGY  Point Mutation  Proteins/IMMUNOLOGY  RNA-Directed
       DNA Polymerase/GENETICS/IMMUNOLOGY  Support, Non-U.S. Gov't  JOURNAL
       ARTICLE

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

