Hierarchy of SPEA presentation to T cells by mouse MHC haplotypes

The ability of splenic antigen-presenting cells (APC) from nine independent mouse major histocompatibility complex (MHC) haplotypes to present recombinant streptococcal exotoxin A (rSPEA) to heterogeneous T cells and mouse T cell clones were compared using proliferation assays. We report that there is marked variation between MHC haplotypes, which can be ranked as follows: H2z > H2s = H2f = H2p = H2r = H2k > H2d > H2b = H2q. In some haplotypes both A and E molecules bind rSPEA with low affinity. In addition, we show that presentation is preferentially by E molecules in haplotypes where A and E are coexpressed, but that A alleles also bind and present rSPEA, based on inhibition of responses by anti-E and anti-A mAbs. Furthermore, using strains of mice which fail to express E, we demonstrate that A(s) and Af present rSPEA with high efficiency, whereas Aq and Ab are the least efficient of all haplotypes. The results suggest that there is significant variation in the ability of different alleles of both E and A molecules to bind and present rSPEA.