MHC class Ib-restricted CTL provide protection against primary and secondary Listeria monocytogenes infection

Infection of B6 mice with the intracellular pathogen Listeria monocytogenes (LM) results in the activation of CD8(+) T cells that respond to Ag presen ted by both MHC class Ia and class Ib molecules. Enzyme-linked immunospot a nalysis reveals that these CTL populations expand and contract at different times following a primary sublethal LM infection. Between days 4 and 6 pos tinfection, class Ib-restricted CTL exhibit a rapid proliferative response that is primarily H2-M3 restricted. The peak response of class Ia-restricte d CD8(+) T cells occurs a few days later, after the majority of bacteria ha ve been cleared. Although class Ia-restricted CTL exhibit a vigorous recall response to secondary LM infection, we observe limited expansion of class Tb-restricted memory CTL, even in MHC class Ia-deficient mice (B6.Kb-/-Db-/ -). Despite this lack of enhanced expansion in vivo, class Ib-restricted me mory CTL retain the ability to proliferate and expand when provided with Ag in vitro. Furthermore, we demonstrate that in vivo depletion of CD8(+) T c ells in LM-immune E6.Kb(-/-)Db(-/-) mice severely impairs memory protection . Together, these data demonstrate that class Ib-restricted CTL play an imp ortant role in clearing a primary LM infection and generate a memory popula tion capable of providing significant protection against subsequent infecti on.