The Role of Amino Acid Position and Side Chain Structure in Serological and CTL-Defined Epitopes on the HLA-A2.1 Molecule

  • K. T. Hogan
  • C. Clayberger
  • N. Shimojo
  • W. E. Biddison
  • A. M. Krensky
  • V. H. Engelhard
Conference paper

Abstract

A major focus of current immunological research is to determine the structure-function relationships of class I MHC molecules. The determination of the three-dimensional structure of HLA-A2.1 by Bjorkman et al. (1987a, 1987b) has significantly advanced our ability to achieve this goal. The α3 domain, which composes the membrane proximal region of the molecule, has a structure similar to that of the constant region of immunoglobulin, and primarily associates with β2- microglobulin. The membrane distal region consists of the α1 and α2 domains which interact to form a β-sheet platform, on top of which reside two antiparallel α-helices that are separated by a long groove. It was hypothesized that this groove acts as the binding site for peptides that are recognized by the TCR in association with class I molecules and in fact, an unidentified peptide(s) was associated with this groove in the crystal structure. An analysis of the crystallographic structure of HLA-A2.1 reveals that nearly all of the side chains of the polymorphic residues are oriented such that they point into the groove of the molecule and thus could be important in mediating contact with peptide, or they point upward from the α-helices and may thus be important in interacting with the TCR (Parham et al. 1988).

Keywords

Influenza Val152 Prefix Ferrone Bluestone 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • K. T. Hogan
    • 1
  • C. Clayberger
    • 2
  • N. Shimojo
    • 3
  • W. E. Biddison
    • 3
  • A. M. Krensky
    • 2
  • V. H. Engelhard
    • 4
  1. 1.Department of MicrobiologyMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of PediatricsStanford UniversityStanfordUSA
  3. 3.Neuroimmunology Branch, NINCDSNIHBethesdaUSA
  4. 4.Department of MicrobiologyUniversity of VirginiaCharlottesvilleUSA

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