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M9650294.TXT
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1996-03-09
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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).