In 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.
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.
Lightstone
L
L
Department of Immunology, Commonwealth Building, Royal Postgraduate Medical School, Du Cane Road, London, W12 0NN, England. llightst@rpms.ac.uk
Hargreaves
R
R
Bobek
G
G
Peterson
M
M
Aichinger
G
G
Lombardi
G
G
Lechler
R
R
D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis*; D002460:Cell Line; D000939:Epitopes / Q000032:analysis; D006681:HLA-D Antigens / Q000096:biosynthesis* / Q000276:immunology; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000737:chemistry*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000939:Epitopes; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; C045084:invariant chain