Individual effects of the DR11-variable β-chain residues 67, 71, and 86 upon DR(α,β1*1101)-restricted, peptide-specific T cell proliferation

Jeffrey S. McKinney, Xin Ting Fu, Craig Swearingen, Ellen Klohe, Robert W. Karr

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Abstract

The four members of the HLA-DR11 family of class II molecules vary only by three or fewer amino acids via dimorphisms among DRβ-chain residues 67, 71, and 86. However, they differ markedly in their abilities to induce proliferation of DR(α,β1*1101)-restricted, peptide-specific T cell clones. To dissect which DR11-variable residues, individually and in combination, mediate these functional differences, we used as APC transfectants expressing DR molecules with one of all possible permutations of DR11-variable sequences, including the four DR11 family members, and four additional DR11 variant mutants. The abilities of the wild-type or mutant molecules to present two distinct influenza peptide Ags, HA307-19 and HA128-45, to T cells was assessed in in vitro T cell proliferation assays. Of the naturally dimorphic DR11 positions, residue β 71 variation significantly influenced the ability of DR11 molecules to present both peptides to DR(α,β1*1101)- restricted T cells. Residue β 86 variation had relatively less influence than reported in several other DR and peptide systems. Residue β 67 variation usually appeared irrelevant to T cell proliferation, but in two mutants led to unexpected T cell proliferation independent of nominal peptide Ag. Peptide binding, assessed by flow cytometry, was not found to be altered by any mutations that disrupted DR(α,β1*1101)-like presentation. These data indicate that residue β 71 exerts a central role in influencing the functional differences among DR11 molecules, whereas the widely studied dimorphism of residue β 86 is not as generally influential in DR11 as in other alleles.

Original languageEnglish (US)
Pages (from-to)5564-5571
Number of pages8
JournalJournal of Immunology
Volume153
Issue number12
StatePublished - Dec 15 1994

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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