Critical role of HLA-DRβ1 residue 58 in multiple polymorphic epitopes recognized by xenogeneic and allogeneic antibodies

Ellen Klohe, Maria Pia Pistillo, Giovanni B. Ferrara, Nancy E. Goeken, Nancy S. Greazel, Robert W. Karr

Research output: Contribution to journalArticle

Abstract

In a previous study, we identified glutamic acid at position 58 in DR (β1 * 1101) as critical for the epitopes recognized by the DRw11-specific mAb GS88.2, as well as the I-LR1 mAb that recognizes a polymorphic epitope on DR(α,β1 * 1101) and some DP molecules. The purpose of this study was to determine whether other polymorphic residues contribute to these epitopes and whether DRβ glutamic acid or alanine 58 and DPβ glutamic acid 56, the analogous position in DPβ, contribute to epitopes recognized by other anti-class-II mAb and allosera. Site-directed mutagenesis and transfection were used to produce cells bearing wild-type or mutant class II molecules that were analyzed with mAbs by flow cytometry and with human allosera by absorption and subsequent microcytotoxicity assays. These studies demonstrate that the residue at DRβ position 58 plays a central role in at least three different mAb epitopes and an epitope recognized by anti-DRw11 allosera. Substitution of glutamic acid for alanine at position 58 of eight DRβ chains caused gain of binding of four mAbs to all of the mutant molecules, except DR(α,β4*0101). These data suggest that the side chains of DRβ 58 and DPβ 56 point outward from the α-helix and directly contact antibody.

Original languageEnglish
Pages (from-to)18-28
Number of pages11
JournalHuman Immunology
Volume35
Issue number1
DOIs
Publication statusPublished - 1992

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HLA-DR1 Antigen
Heterophile Antibodies
Epitopes
Glutamic Acid
Alanine
Site-Directed Mutagenesis
Transfection
Flow Cytometry
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Critical role of HLA-DRβ1 residue 58 in multiple polymorphic epitopes recognized by xenogeneic and allogeneic antibodies. / Klohe, Ellen; Pistillo, Maria Pia; Ferrara, Giovanni B.; Goeken, Nancy E.; Greazel, Nancy S.; Karr, Robert W.

In: Human Immunology, Vol. 35, No. 1, 1992, p. 18-28.

Research output: Contribution to journalArticle

Klohe, Ellen ; Pistillo, Maria Pia ; Ferrara, Giovanni B. ; Goeken, Nancy E. ; Greazel, Nancy S. ; Karr, Robert W. / Critical role of HLA-DRβ1 residue 58 in multiple polymorphic epitopes recognized by xenogeneic and allogeneic antibodies. In: Human Immunology. 1992 ; Vol. 35, No. 1. pp. 18-28.
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AU - Greazel, Nancy S.

AU - Karr, Robert W.

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