Human antigen presenting cells express three human leukocyte antigen (HLA) class II isotypes (DR, DP, and DQ), which are composed of polymorphic α and β subunits. The combination of polymorphic α- and β-chains results in cis (encoded on the same chromosome) or trans (encoded on different chromosomes) combinations. Since some of the α-β combinations may yield mismatched non-functional α-β heterodimers, it is not entirely clear which type of HLA class II peptide receptors are found on the cell surface of antigen presenting cells. We have developed a combination of biochemical techniques for inspection of the assembly and intracellular transport of isotype matched and mismatched class II heterodimers.