Relaxed DM requirements during class II peptide loading and CD4+ T cell maturation in BALB/c mice

Current ideas about DM actions have been strongly influenced by studies of mutant strains expressing the H-2(b) haplotype. To evaluate DM contributions to class It activities in BALB/c mice, we generated a novel mutation at the DMa locus via embryonic stem cell technology. Unlike long-lived A(b)/Class II-associated invariant chain-derived peptide (CLIP) complexes, mature A(d) and E-d molecules are loosely occupied by class II-associated invariant chain-derived peptide and are SDS unstable. BALB/c DM mutants weakly express BP107 conformational epitopes and toxic shock syndrome toxin-1 superantigen-binding capabilities, consistent with partial occupancy by wild-type ligands. Near normal numbers of mature CD4(+) T cells fail to undergo superantigen-mediated negative selection, as judged by TCR V beta usage. Ag presentation assays reveal consistent differences for A(d)- and E-d-restricted T cells. Indeed, the mutation leads to decreased peptide capture by A(d) molecules, and in striking contrast causes enhanced peptide loading by E-d molecules. Thus, DM requirements differ for class II structural variants coexpressed under physiological conditions in the intact animal. The Journal of Immunology 2001.