We have generated mice lacking H2-M complexes, critical facilitators of peptide loading onto major histo-compatibility complex class II molecules. Ab molecules in these mice matured into stable complexes and were efficiently expressed at the cell surface. Most carried a single peptide derived from the class II-associated invariant chain; the diverse array of peptides normally displayed by class II molecules was absent. Cells from mutant mice presented both whole proteins and short peptides very poorly. Surprisingly, positive selection of CD4+ T cells was quite efficient, yielding a large and broad repertoire. Peripheral T cells reacted strongly to splenocytes from syngeneic wild-type mice, no doubt reflecting the unique peptide complement carried by class II molecules in mutant animals.

According to past reports, H-2Ma0/0 mice express a single major histocompatiblity complex class II molecule, A(b), heavily loaded with a single peptide derived from the invariant chain, CLIP. Despite the highly restricted diversity of the class II:peptide complexes expressed on thymic stromal cells in the mutant animals, a large and diverse population of CD4+ T cells is positively selected. However, two important issues remained unresolved and are addressed here: Just how preponderant is CLIP occupancy of the class II molecules from H-2M0/0 mice? How extensive and functionally competent is the CD4+ population selected in the mutant animals? Our results argue that a single class II:peptide complex can select a very broad, though not complete, repertoire of CD4+ T cells.