Open AccessIn the absence of the invariant chain, HLA-DR molecules display a distinct array of peptides which is influenced by the presence or absence of HLA-DM
Author(s) -
Liz Lightstone,
Roseanna Hargreaves,
Gabriele Bobek,
Mary Peterson,
Gerald Aichinger,
Giovanna Lombardi,
Robert I. Lechler
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.11.5772
Subject(s) - allorecognition , peripheral blood mononuclear cell , major histocompatibility complex , biology , human leukocyte antigen , t cell , microbiology and biotechnology , transfection , hla dr , histocompatibility , antigen , immunology , in vitro , cell culture , genetics , immune system
The independent influences of invariant chain (Ii) and HLA-DM molecules on the array of naturally processed peptides displayed by HLA-DR molecules were studied using transfected cell lines. The absence of Ii led to an altered set of HLA-DR-bound peptides as judged by the discriminating responses of alloreactive T cell clones. While most T cell clones raised against DR+Ii+DM+ peripheral blood mononuclear cells (PBMC) failed to respond to DR+Ii-DM- cells, T cell clones raised against DR+Ii-DM- transfectants were not stimulated by DR+Ii+DM+ cells. Furthermore, coexpression of HLA-DM with HLA-DR1 in the absence of Ii augmented responses of anti-PBMC T cell clones but inhibited allorecognition by T cell clones raised against DR+Ii-DM- transfectants. The conformational integrity of the class II molecules, as judged by serology, suggests that the patterns of reactivity of the T cell clones reflect specificity for different alloantigen-bound peptides. Hence, discordant regulation of expression of major histocompatibility complex class II, Ii, and HLA-DM molecules in vivo may lead to the display of novel self-peptides and possible interruption of self-tolerance.