Examination of HY response: T cell expansion, immunodominance, and cross-priming revealed by HY tetramer analysis

We have applied MHC class I tetramers representing the two H2(b) MHC class I-restricted epitopes of the mouse male-specific minor transplantation Ag, HY, to directly determine the extent of expansion and immunodominance withi n the CD8(+) T cell compartment following exposure to male tissue. Immuniza tion with male bone marrow (BM), spleen, dendritic cells (DCs) and by skin graft led to rapid expansion of both specificities occupying up to >20% of the CD8(+) T cell pool. At a high dose, whole BM or spleen were found to be more effective at stimulating the response than BM-derived DCs. In vivo, i mmunodominance within the responding cell population was only observed foll owing chronic Ag stimulation, whereas epitope immunodominance was establish ed rapidly following in vitro restimulation. Peptide affinity for the restr icting MHC molecule was greater for the immunodominant epitope, suggesting that this might be a factor in the emergence of immunodominance. Using tetr amers, we were able to directly visualize the cross-primed CD8(+) HY respon se, but we did not find it to be the principal route for MHC class I presen tation. Immunization with female spleen or DCs coated with the full complem ent of defined HY peptides, including the A(b)-restricted CD4(+) Th cell de terminant, failed to induce tetramer-reactive cells.