Relationship between kinetic stability and immunogenicity of HLA-DR4/peptide complexes.

Abstract:

:Immunodominant T cell epitopes from the autoantigen human cartilage glycoprotein 39 have previously been mapped in the context of HLA-DR*0401 and *0402, using mice expressing HLA-DR4 transgenes. We measured the dissociation rates of these epitopes from soluble recombinant DR*0401 and DR*0402 to assess the relationship between peptide/HLA-DR4 kinetic stability and immunogenicity. Experiments were performed at endosomal pH (5.5) and at cell surface pH (7), in the absence and presence of soluble recombinant HLA-DM (sDM). All (4/4) immunodominant peptide/HLA-DR complexes exhibit dissociation half-times of 1h to several days. In contrast, most (3/4) non-immunodominant complexes dissociate with half-times <30 min under at least one of these conditions. Interestingly, a complex which is stable except in the presence of HLA-DM at pH 5.5 is immunogenic only following peptide immunization, while a complex which is stable at acidic but not at neutral pH, is non-immunogenic following either whole protein or peptide immunization. These data indicate that kinetic stability of peptide/MHC complexes in vivo is a key determinant of immunogenicity.

journal_name

Eur J Immunol

authors

Hall FC,Rabinowitz JD,Busch R,Visconti KC,Belmares M,Patil NS,Cope AP,Patel S,McConnell HM,Mellins ED,Sonderstrup G

doi

10.1002/1521-4141(200203)32:3<662::AID-IMMU662>3.0

keywords:

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

662-70

issue

3

eissn

0014-2980

issn

1521-4141

journal_volume

32

pub_type

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