Immunogenetics

, Volume 40, Issue 1, pp 9–20 | Cite as

The minimal polymorphism of class II Eα chains is not due to the functional neutrality of mutations

  • Zy-Ting E. Chu
  • C. Carswell-Crumpton
  • Barry C. Cole
  • Patricia P. Jones
Original Paper

Abstract

Given the extensive allelic amino acid sequence polymorphism present in the first domain of Aα, Aβ, and Eβ chains and its profound effects on class II function, the minimal polymorphism in the mouse Eα chain (and in its human homologue DRα) is paradox. Two possible explanations for the lack of polymorphism in Eα are: (1) the Eα chain plays such a uniquely critical structural/functional role in antigen presentation, T-cell activation, repertoire selection, and/or pairing with Eβ or other proteins for expression that it cannot vary, and mutations are selected against; (2) the Eα chain plays a less significant role than the outer domains of other major histocompatibility complex (MHC) proteins in determining the interactions with processed peptides or with T-cell receptor (TCR), so there is no selective pressure to maintain new mutations. To explore this question we compared the ability of transfectants expressing wild type (wt) EαEβd and mutant Eα wt Eβd proteins to present peptides and bacterial superantigens to T-cell hybridomas. Mutations at the Eα amino acid positions 31, 52, and 65&66, to residues that represent allelic alternatives in Aα chains, significantly reduced activation of peptide-specific T hybridomas, and mutations at 71 sometimes enhanced T-cell stimulation. None of the Eα mutations reduced, and some enhanced, superantigen stimulation of T-cell hybridomas. These results argue against the hypothesis that Eα chains are minimally polymorphic because mutations in Eα are functionally neutral.

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Zy-Ting E. Chu
    • 1
  • C. Carswell-Crumpton
    • 1
  • Barry C. Cole
    • 2
  • Patricia P. Jones
    • 1
  1. 1.Department of Biological SciencesStanford UniversityStanfordUSA
  2. 2.Department of Internal MedicineUniversity of Utah Medical CenterSalt Lake CityUSA

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