IN THE ABSENCE OF THE INVARIANT CHAIN, HLA-DR MOLECULES DISPLAY A DISTINCT ARRAY OF PEPTIDES WHICH IS INFLUENCED BY THE PRESENCE OR ABSENCEOF HLA-DM

The independent influences of invariant chain (Ii) and HLA-DM molecule s on the array of naturally processed peptides displayed by HLA-DR mol ecules were studied using transfected cell lines, The absence of Ii le d to an altered set of HLA-DR-bound peptides as judged by the discrimi nating responses of alloreactive T cell clones, While most T cell clon es 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 inhi bited 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 th e T cell clones reflect specificity for different alloantigen-bound pe ptides, Hence, discordant regulation of expression of major histocompa tibility complex class II, Ii, and HLA-DM molecules in vivo may lead t o the display of novel self-peptides and possible interruption of self -tolerance.