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

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.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Drover S,Kovats S,Masewicz S,Blum JS,Nepom GT

doi

10.1016/s0198-8859(97)00263-2

subject

Has Abstract

pub_date

1998-02-01 00:00:00

pages

77-86

issue

2

eissn

0198-8859

issn

1879-1166

pii

S0198885997002632

journal_volume

59

pub_type

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