CD8+ T-Cell Responses to Trypanosoma cruzi Are Highly Focused on Strain-Variant trans-Sialidase Epitopes

PLoS Pathogens

Mark Heiges¹  Diana L Martin¹  D. Brent Weatherly¹  Charles S Rosenberg¹  Alessandro Sette²  Matthew T Crim²  Susan Sullivan²  Sarah H Craven³  Melissa A Cabinian³  Matthew H Collins³  Susana A Laucella⁴  Rick L Tarleton⁴  Miriam Postan⁵ 

[1] Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, United States of America;Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America;Department of Microbiology, University of Georgia, Athens, Georgia, United States of America;Instituto Nacional de Parasiologia Dr. Mario Fatala Chaben/Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS/Malbran), Buenos Aires, Argentina;La Jolla Institute for Allergy and Immunology, San Diego, California, United States of America

关键词: T cells;    Cytotoxic T cells;    Trypanosoma cruzi;    Parasitic diseases;    Immune response;    Protozoan infections;    Mammalian genomics;    Parasitic protozoans;   

DOI  :  10.1371/journal.ppat.0020077

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

CD8+ T cells are crucial for control of a number of medically important protozoan parasites, including Trypanosoma cruzi, the agent of human Chagas disease. Yet, in contrast to the wealth of information from viral and bacterial infections, little is known about the antigen specificity or the general development of effector and memory T-cell responses in hosts infected with protozoans. In this study we report on a wide-scale screen for the dominant parasite peptides recognized by CD8+ T cells in T. cruzi–infected mice and humans. This analysis demonstrates that in both hosts the CD8+ T-cell response is highly focused on epitopes encoded by members of the large trans-sialidase family of genes. Responses to a restricted set of immunodominant peptides were especially pronounced in T. cruzi–infected mice, with more than 30% of the CD8+ T-cell response at the peak of infection specific for two major groups of trans-sialidase peptides. Experimental models also demonstrated that the dominance patterns vary depending on the infective strain of T. cruzi, suggesting that immune evasion may be occurring at a population rather than single-parasite level.

【 授权许可】

CC BY