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PMID: 15037737 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Conserved T cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 14 ·2004-04-06 ·Pages 4942-7

Kedzierska K, Turner SJ, Doherty PC

Abstract

The CD8+ T cell response to the immunodominant DbNP366 epitope has been analyzed sequentially to determine the prevalence and persistence of different T cell antigen receptor (TCR)Vbeta8.3 clonotypes after primary and secondary influenza virus challenge. Based on the length and amino acid sequences of the complementarity-determining region 3 of TCRbeta (CDR3beta) loop and associated Jbeta usage, the same dominant TCRbeta signatures were found in the blood, the spleen, and the site of virus-induced pathology in the infected respiratory tract. Longitudinal analysis demonstrated that TCRbeta prominent in the antigen-driven phase of response persisted into memory and were again expanded after secondary challenge. A proportion of these high-frequency TCRbeta expressed "public" CDR3beta sequences that were detected in every mouse sampled, whereas others were found more than once but were not invariably present. Analysis of N-region nucleotide diversity established that as many as 10 different nucleic acid sequences (maximum of four "nucleotypes" in any one mouse) could encode a single public TCRbeta amino acid sequence. Conversely, whereas some of the unique, "private" TCRbeta achieved a substantial clone size, they were always specified by a single nucleotype. Although there is a strong stochastic element in this response, the public TCRbeta seem to represent a "best fit" for this immunodominant epitope, are selected preferentially from the naive TCR repertoire, and assume even greater prominence after secondary challenge.

MeSH Terms
Amino Acid Sequence Animals Base Sequence DNA Primers Female Immunodominant Epitopes/chemistry,immunology Immunologic Memory Influenza A virus/immunology Mice Mice, Inbred C57BL Nucleoproteins/chemistry,immunology Receptors, Antigen, T-Cell, alpha-beta/immunology Reverse Transcriptase Polymerase Chain Reaction
Chemicals
DNA Primers Immunodominant Epitopes Nucleoproteins Receptors, Antigen, T-Cell, alpha-beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kedzierska Katherine
Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia.
Turner Stephen J
Doherty Peter C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0401279101
Published
2004-04-06
Epub
2004-00-22
Pages
4942-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC387353
Subset
IM
Grants
NIAID NIH HHS · R37 AI029579 · United States
NIAID NIH HHS · AI29579 · United States
External Links
PubMed source DOI: 10.1073/pnas.0401279101 PMC Full Text View journal details
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