A rodent comprising at a first endogenous MHC II locus, a nucleotide sequence encoding a first chimeric human/rodent MHC II α polypeptide and a nucleotide sequence encoding a first chimeric human/rodent MHC II β polypeptide, wherein the first chimeric human/rodent MHC II α polypeptide comprises α1 and α2 domains of a human HLA-DR α polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II α polypeptide, wherein the first chimeric human/rodent MHC II β polypeptide comprises β1 and β2 domains of a human HLA-DR β polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II β polypeptide, and wherein the first chimeric human/rodent MHC II α polypeptide and the first chimeric human/rodent MHC II β polypeptide form a first MHC II complex on a surface of a cell of the rodent; and at a second endogenous MHC II locus, a nucleotide sequence encoding a second chimeric human/rodent MHC II α polypeptide and a nucleotide sequence encoding a second chimeric human/rodent MHC II β polypeptide, wherein the second chimeric human/rodent MHC II α polypeptide comprises α1 and α2 domains of a human HLA-DQ α polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II α polypeptide, wherein the second chimeric human/rodent MHC II β polypeptide comprises β1 and β2 domains of a human HLA-DQ β polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II β polypeptide, and wherein the second chimeric human/rodent MHC II α polypeptide and the second chimeric human/rodent MHC II β polypeptide form a second MHC II complex on a surface of a cell of the rodent. at a first endogenous MHC II locus, a nucleotide sequence encoding a first chimeric human/rodent MHC II α polypeptide and a nucleotide sequence encoding a first chimeric human/rodent MHC II β polypeptide, wherein the first chimeric human/rodent MHC II α polypeptide comprises α1 and α2 domains of a human HLA-DR α polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II α polypeptide, wherein the first chimeric human/rodent MHC II β polypeptide comprises β1 and β2 domains of a human HLA-DR β polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II β polypeptide, and wherein the first chimeric human/rodent MHC II α polypeptide and the first chimeric human/rodent MHC II β polypeptide form a first MHC II complex on a surface of a cell of the rodent; and wherein the first chimeric human/rodent MHC II α polypeptide comprises α1 and α2 domains of a human HLA-DR α polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II α polypeptide, wherein the first chimeric human/rodent MHC II β polypeptide comprises β1 and β2 domains of a human HLA-DR β polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II β polypeptide, and wherein the first chimeric human/rodent MHC II α polypeptide and the first chimeric human/rodent MHC II β polypeptide form a first MHC II complex on a surface of a cell of the rodent; and at a second endogenous MHC II locus, a nucleotide sequence encoding a second chimeric human/rodent MHC II α polypeptide and a nucleotide sequence encoding a second chimeric human/rodent MHC II β polypeptide, wherein the second chimeric human/rodent MHC II α polypeptide comprises α1 and α2 domains of a human HLA-DQ α polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II α polypeptide, wherein the second chimeric human/rodent MHC II β polypeptide comprises β1 and β2 domains of a human HLA-DQ β polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II β polypeptide, and wherein the second chimeric human/rodent MHC II α polypeptide and the second chimeric human/rodent MHC II β polypeptide form a second MHC II complex on a surface of a cell of the rodent. wherein the second chimeric human/rodent MHC II α polypeptide comprises α1 and α2 domains of a human HLA-DQ α polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II α polypeptide, wherein the second chimeric human/rodent MHC II β polypeptide comprises β1 and β2 domains of a human HLA-DQ β polypeptide operably linked to transmembrane and cytoplasmic domains of an endogenous rodent MHC II β polypeptide, and wherein the second chimeric human/rodent MHC II α polypeptide and the second chimeric human/rodent MHC II β polypeptide form a second MHC II complex on a surface of a cell of the rodent.