Abstract:
:By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with major histocompatibility complex class II molecules. Alternative pathways of epitope production have been identified, but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome and γ-interferon-inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses.
journal_name
Nat Medjournal_title
Nature medicineauthors
Miller MA,Ganesan AP,Luckashenak N,Mendonca M,Eisenlohr LCdoi
10.1038/nm.3958subject
Has Abstractpub_date
2015-10-01 00:00:00pages
1216-22issue
10eissn
1078-8956issn
1546-170Xpii
nm.3958journal_volume
21pub_type
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