Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses.

Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. Research Abstract Details 

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Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. Abstract Text:

Paul G Thomas,Scott A Brown,Rachael Keating,Wen Yue,Melissa Y Morris,Jenny So,Richard J Webby,Peter C Doherty,

Influenza A virus-specific CD8+ T cell responses in H2(b) mice are characterized by reproducible hierarchies. Compensation by the D(b)PB1-F2(62) epitope is apparent following infection with a variant H3N2 virus engineered to disrupt the prominent D(b)NP(366) and D(b)PA(224) epitopes (a double knockout or DKO). Analysis with a "triple" knockout (TKO) virus, which also compromises D(b)PB1-F2(62), did not reveal further compensation to the known residual, minor, and predicted epitopes. However, infection with this deletion mutant apparently switched protective immunity to an alternative Ab-mediated pathway. As expected, TKO virus clearance was significantly delayed in Ab-deficient MHC class II(-/-) and Ig(-/-) mice, which were much more susceptible following primary, intranasal infection with the TKO, but not DKO, virus. CD8+ T cell compensation was detected in DKO, but not TKO, infection of Ig-deficient mice, suggestive of cooperation among CD8+ T cell responses. However, after priming with a TKO H1N1 mutant, MHC II(-/-) mice survived secondary intranasal exposure to the comparable H3N2 TKO virus. Such prime/challenge experiments with the DKO and TKO viruses allowed the emergence of two previously unknown epitopes. The contrast between the absence of compensatory effect following primary exposure and the substantial clonal expansion after secondary challenge suggests that the key factor limiting the visibility of these "hidden" epitopes may be very low naive T cell precursor frequencies. Overall, these findings suggest that vaccine approaches using virus vectors to deliver an Ag may be optimized by disrupting key peptides in the normal CD8+ T cell response associated with common HLA types.

Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. Publishing Authors By Initials

PG Thomas,SA Brown,R Keating,W Yue,MY Morris,J So,RJ Webby,PC Doherty,

For similar biological phenomena, cell phenomena, and immunity: immunity: antibody specificity: species specificity research abstracts see: biological phenomena, cell phenomena, and immunity: immunity: antibody specificity: species specificity research

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Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 178

Page Numbers: 3091-8

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 1

MONTH: Mar

YEAR: 2007

Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. Keywords Mesh Terms:

KEYWORDS: Species Specificity

MESH TERMS: immunology

Chemical & Substance for Abstract: Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. Information

Substance Name: Peptides

Registry Number: 0

Grant and Affiliation Information for Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses.

AFFILIATION: Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105, USA.

Country: United States

AGENCY: United States NIAID

GRANT: AI 95357

ACRONYM: AI

MEDLINETA: J Immunol

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