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

First Author  Bikoff EK Year  2001
Journal  J Immunol Volume  166
Issue  8 Pages  5087-98
PubMed ID  11290790 Mgi Jnum  J:113714
Mgi Id  MGI:3687462 Doi  10.4049/jimmunol.166.8.5087
Citation  Bikoff EK, et al. (2001) Relaxed DM requirements during class II peptide loading and CD4+ T cell maturation in BALB/c mice. J Immunol 166(8):5087-98
abstractText  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 II 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 Vbeta 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.
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