Immunodominant and subdominant CTL responses to Listeria monocytogenes infection.
Protective immunity to infection by intracellular pathogens begins with expansion of Ag-specific, effector T lymphocytes and is followed by persistence of pathogen-specific memory T cells. Infection by Listeria monocytogenes, an intracellular bacterium, induces cytolytic T lymphocytes that mediate systemic sterilization and long term immunity. In cells infected with L. monocytogenes, H2-Kd class I molecules present three nonamer peptides, listeriolysin (LLO) 91-99, p60 217-225, and p60 449-457, to CTL. Herein we show that during the peak CTL response to L. monocytogenes infection, the ratio of T cells specific for LLO 91-99, p60 217-225, and p60 449-457 is approximately 20:10:1, respectively. While the number of Ag-specific T lymphocytes decreases in the weeks after infection, the proportion of T lymphocytes specific for the three epitopes is maintained. Repertoire analysis of a subset of L. monocytogenes-specific T cells, using alanine-substituted variants of p60 217-225, indicates that the range of T cell specificities is maintained by memory cells. These results indicate that the breadth and relative magnitude of T cell specificities initially elicited by an infection are transmitted to the memory compartment. Our results suggest that T lymphocytes with different gross and fine Ag specificities are equally likely to become memory T cells.
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Section of Infectious Diseases, Yale University, New Haven, CT 06520, USA.
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D000208:Acute Disease; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002469:Cell Separation; D002999:Clone Cells; D004797:Enzyme-Linked Immunosorbent Assay; D016056:Immunodominant Epitopes / Q000276:immunology*; D007156:Immunologic Memory; D008088:Listeriosis / Q000276:immunology* / Q000517:prevention & control; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000942:Antigens, Bacterial; D016056:Immunodominant Epitopes