MHC class la-restricted memory T cells inhibit expansion of a nonprotective MHC class Ib (H2-M3)-restricted memory respose

Listeria monocytogenes infection generates major histocompatibility complex (MHC) class Ia-restricted and MHC class Ib-(H2-M3)-restricted effector and memory CD8⁺ T cells. However, only MHC class Ia-restricted memory cells expand after rechallenge, and it is unknown if MHC class Ib-restricted memory CD8⁺ T cells generated by vaccination are protective. We show here that H2-M3-restricted memory CD8⁺ T cells were capable of secondary expansion but, in contrast to primary H2-M3-restricted effector cells, failed to provide protective immunity. In LM-immune mice, MHC class Ia-restricted memory CD8⁺ T cells prevented the expansion of H2-M3-restricted memory T cell populations by limiting dendritic cell antigen presentation. Thus, protective immunity by H2-M3-resricted T cells is limited to primary infection, indicating that memory MHC class Ia-restricted T cells prevent nonessential immune responses during secondary infection.