MICE LACKING H2-M COMPLEXES, ENIGMATIC ELEMENTS OF THE MHC CLASS-II PEPTIDE-LOADING PATHWAY

We have generated mice lacking H2-M complexes, critical facilitators o f peptide loading onto major histocompatibility complex class II molec ules. Ab molecules in these mice matured into stable complexes and wer e efficiently expressed at the cell surface. Most carried a single pep tide 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 pepti des very poorly. Surprisingly, positive selection of CD4(+) T cells wa s 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.