Modulation of peptide-dependent allospecific epitopes on HLA-DR4 molecules by HLA-DM

Sheila Drover, Susan Kovats, Susan Masewicz, Janice Blum, Gerald T. Nepom

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Peptide binding to HLA-DR molecules in intracellular compartments is facilitated by HLA-DM molecules, present in most types of antigen-presenting cells. Allorecognition of DR specificities represents a form of T cell recognition of the MHC-peptide complex which in some cases is influenced by peptide binding. DRA and DRB*0401 (Dw4) genes were introduced into different cell types including DM-negative and DM-restored mutant cells to analyze recognition of DR4 subtypes by alloreactive T cell clones and Dw4-specific monoclonal antibodies. Distinct patterns of T cell recognition were identified: (i) deficient response to Dw4 molecules in the absence of DM expression in which T cell responses were restored by transfecting DM into the Dw4-expressing cells; and (ii) equivalent recognition of Dw4 on DM- and DM+ cells. Using several mAb to Dw4 molecules, a similar distinction was observed: a shared epitope on Dw4 and Dw14 molecules was partially DM- independent while a Dw4-specific epitope was DM-dependent and cell type- specific. Thus, a subset of both T cell and mAb allodeterminants are influenced by a DM-dependent interaction of MHC molecules with peptides, while the formation of DM-independent allodeterminants may represent direct MHC epitope recognition by the T cell receptor or an alternative peptide loading mechanism distinct from the HLA-DM pathways.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalHuman Immunology
Volume59
Issue number2
DOIs
StatePublished - Feb 1998

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HLA-DR4 Antigen
Epitopes
Peptides
T-Lymphocytes
Dichlororibofuranosylbenzimidazole
T-Lymphocyte Subsets
HLA-DR Antigens
Antigen-Presenting Cells
T-Cell Antigen Receptor
Clone Cells
Monoclonal Antibodies
Genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Modulation of peptide-dependent allospecific epitopes on HLA-DR4 molecules by HLA-DM. / Drover, Sheila; Kovats, Susan; Masewicz, Susan; Blum, Janice; Nepom, Gerald T.

In: Human Immunology, Vol. 59, No. 2, 02.1998, p. 77-86.

Research output: Contribution to journalArticle

Drover, Sheila ; Kovats, Susan ; Masewicz, Susan ; Blum, Janice ; Nepom, Gerald T. / Modulation of peptide-dependent allospecific epitopes on HLA-DR4 molecules by HLA-DM. In: Human Immunology. 1998 ; Vol. 59, No. 2. pp. 77-86.
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