Document 0715
 DOCN  M9440715
 TI    Analysis of mutant HLA-A2 molecules. Differential effects on peptide
       binding and CTL recognition.
 DT    9404
 AU    Tussey LG; Matsui M; Rowland-Jones S; Warburton R; Frelinger JA;
       McMichael A; Institute of Molecular Medicine, John Radcliffe Hospital,
       Oxford,; UK.
 SO    J Immunol. 1994 Feb 1;152(3):1213-21. Unique Identifier : AIDSLINE
       MED/94132617
 AB    Previous studies have identified several residues lining the groove of
       the HLA-A2.1 molecule that are critical for Ag presentation. However, it
       is not clear whether these residues are critical for binding of the
       peptide epitope per se or for determining the appropriate conformation
       of bound peptide. To distinguish between these possibilities, mutations
       at eight of these residues have been tested for their effects on the
       ability of the molecule to bind and present two known peptide
       epitopes--one derived from the influenza A matrix protein, the other
       from HIV pol. With only one exception, the mutations were found to
       affect the binding of the two peptides similarly. Most of the mutations
       resulted in intermediate deleterious effects on binding, with the B
       pocket mutant F9Y having the most dramatic negative effect on binding
       for both peptides. Two of the mutations significantly enhanced binding
       of both peptides and a peptide-specific effect on binding was seen with
       the substitution, Y99H, which enhanced binding of the matrix peptide yet
       diminished binding of the pol peptide. In contrast to the effects on
       binding, the effects of the mutations on presentation differed
       considerably for the two peptides. The most striking difference was seen
       with two alpha 2 alpha helix mutants that are fully recognized by pol
       peptide-specific CTL but not recognized by matrix peptide-specific CTL
       even though levels of binding were comparably diminished for the two
       peptides. These results suggest that some interactions, although not
       critical for binding per se, are critical for functional binding and the
       importance of these interactions differs among peptide epitopes.
 DE    Amino Acid Sequence  Antigen-Presenting Cells/IMMUNOLOGY  Binding Sites
       Gene Products, pol/CHEMISTRY/*IMMUNOLOGY  Human  HIV Antigens/*CHEMISTRY
       HLA-A2 Antigen/*CHEMISTRY/GENETICS  In Vitro  Molecular Sequence Data
       Peptides/CHEMISTRY/*IMMUNOLOGY  Protein Structure, Tertiary
       Structure-Activity Relationship  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  T-Lymphocytes, Cytotoxic/*IMMUNOLOGY  JOURNAL ARTICLE

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