Acidic residues in the DRβ chain third hypervariable region are required for stimulation of a DR(α,β1*0402)-restricted T-cell clone

Richard R. Olson, Jeffrey J. Reuter, Janet McNicholl, Carol Alber, Ellen Klohe, Kevin Callahan, Robert F. Siliciano, Robert W. Karr

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the minimal requirements for stimulation of an antigen-specific HLA-DR(α,β1*0402)-restricted T-cell clone (Een 217) by using transfectants expressing mutant DRβ chains as APCs. Antigen-specific stimulation of Een217 was induced with transfectants expressing DR(α,β1*0402) and DR(α,β1*0403) but not other DR4 subtypes that also bind the peptide recognized by this clone. Analysis of the effects of single amino acid substitutions in the β chains of each of the DR4 subtypes revealed a requirement for acidic residues in the third HVR, particularly amino acid 71, in stimulation of clone Een217. Functional class II Mutants were generated from nonstimulatory DR4 subtype β chains by acidic residue substitutions within the third HVR. These data define the requirement for negatively charged residues in this region for peptide-induced stimulation of this T-cell clone. The required acidic residues can be located at either position 70, 71, or 74 in the DRβ chain. The negative charge in this segment of the DRβ chain α-helix may be required for direct interactions with the T-cell receptor of Een217 or may affect peptide conformation.

Original languageEnglish (US)
Pages (from-to)193-200
Number of pages8
JournalHuman Immunology
Volume41
Issue number3
DOIs
StatePublished - Nov 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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