THE REQUIREMENT FOR DM IN CLASS II-RESTRICTED ANTIGEN PRESENTATION AND SDS-STABLE DIMER FORMATION IS ALLELE-DEPENDENT AND SPECIES-DEPENDENT

Recently several cell lines have been identified with mutations in a m ajor histocompatibility complex (MHC)-linked protein that lead to defe cts in class II-restricted antigen presentation and a defect in the fo rmation of class II SDS-stable dimers. The defect in these cells has r ecently been shown to result from the inability to express the MHC-enc oded nonclassical class II molecule called DM. To further examine the role of DM in class II-restricted antigen presentation, we asked if th is defect would equally affect different allelic and species variants of class II molecules. To investigate this, we transfected the parent cell lines T1 and 8.1.6 and their respective antigen presentation muta nts T2 and 9.5.3 with the genes encoding I-A(d) and examined the deriv ed transfectants for their ability to present antigen, the conformatio n of I-A(d) to associate and dissociate with Ii. Surprisingly, these s tudies also revealed that the antigen presentation defect observed for DR in the 9.5.3 cells did not compromise I-A(d)-restricted antigen pr esentation. In addition, we found that the level of SDS-stable dimer f ormation did not correlate with antigen presentation capacity for I-A( d) and that the amount of SDS-stable I-A(d) dimer depends on the cellu lar context in which the class II molecule is expressed. Our results s uggest that the ability to form SDS-stable dimer is not strictly corre lated with class II-restricted antigen presentation. Finally, when two allelic forms of murine class II molecules were compared in the defec tive T2 cell line, it was found that I-A(k) but not I-A(d) forms SDS-s table dimers equivalent to that seen in the parental cell lines. Overa ll, our results suggest that DM may modulate rather than play a requis ite role in I-A(d)-restricted antigen presentation and SDS-stable dime r formation and that dependency on DM may be allele or species specifi c.