Different vaccine vectors delivering the same antigen elicit CD8 + T cell responses with distinct clonotype and epitope specificity

Mitsuo Honda, Rui Wang, Wing Pui Kong, Masaru Kanekiyo, Wataru Akahata, Ling Xu, Kazuhiro Matsuo, Kannan Natarajan, Howard Robinson, Tedi E. Asher, David A. Price, Daniel C. Douek, David H. Margulies, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8+ cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8+ T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2Dd better than the native sequences, and clones with distinct specificities were elicited by alternative vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8+ T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.

Original languageEnglish (US)
Pages (from-to)2425-2434
Number of pages10
JournalJournal of Immunology
Volume183
Issue number4
DOIs
StatePublished - Aug 15 2009
Externally publishedYes

Fingerprint

CD8 Antigens
Epitopes
Vaccines
T-Lymphocytes
Peptides
HIV-1
Immunization
Tuberculosis Vaccines
Genes
Malaria Vaccines
AIDS Vaccines
X Ray Crystallography
Immunity
Vaccination
Clone Cells
Population

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Different vaccine vectors delivering the same antigen elicit CD8 + T cell responses with distinct clonotype and epitope specificity. / Honda, Mitsuo; Wang, Rui; Kong, Wing Pui; Kanekiyo, Masaru; Akahata, Wataru; Xu, Ling; Matsuo, Kazuhiro; Natarajan, Kannan; Robinson, Howard; Asher, Tedi E.; Price, David A.; Douek, Daniel C.; Margulies, David H.; Nabel, Gary J.

In: Journal of Immunology, Vol. 183, No. 4, 15.08.2009, p. 2425-2434.

Research output: Contribution to journalArticle

Honda, M, Wang, R, Kong, WP, Kanekiyo, M, Akahata, W, Xu, L, Matsuo, K, Natarajan, K, Robinson, H, Asher, TE, Price, DA, Douek, DC, Margulies, DH & Nabel, GJ 2009, 'Different vaccine vectors delivering the same antigen elicit CD8 + T cell responses with distinct clonotype and epitope specificity', Journal of Immunology, vol. 183, no. 4, pp. 2425-2434. https://doi.org/10.4049/jimmunol.0900581
Honda, Mitsuo ; Wang, Rui ; Kong, Wing Pui ; Kanekiyo, Masaru ; Akahata, Wataru ; Xu, Ling ; Matsuo, Kazuhiro ; Natarajan, Kannan ; Robinson, Howard ; Asher, Tedi E. ; Price, David A. ; Douek, Daniel C. ; Margulies, David H. ; Nabel, Gary J. / Different vaccine vectors delivering the same antigen elicit CD8 + T cell responses with distinct clonotype and epitope specificity. In: Journal of Immunology. 2009 ; Vol. 183, No. 4. pp. 2425-2434.
@article{474397e6e776458a9fee9da03c6d657c,
title = "Different vaccine vectors delivering the same antigen elicit CD8 + T cell responses with distinct clonotype and epitope specificity",
abstract = "Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8+ cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8+ T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2Dd better than the native sequences, and clones with distinct specificities were elicited by alternative vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8+ T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.",
author = "Mitsuo Honda and Rui Wang and Kong, {Wing Pui} and Masaru Kanekiyo and Wataru Akahata and Ling Xu and Kazuhiro Matsuo and Kannan Natarajan and Howard Robinson and Asher, {Tedi E.} and Price, {David A.} and Douek, {Daniel C.} and Margulies, {David H.} and Nabel, {Gary J.}",
year = "2009",
month = "8",
day = "15",
doi = "10.4049/jimmunol.0900581",
language = "English (US)",
volume = "183",
pages = "2425--2434",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Different vaccine vectors delivering the same antigen elicit CD8 + T cell responses with distinct clonotype and epitope specificity

AU - Honda, Mitsuo

AU - Wang, Rui

AU - Kong, Wing Pui

AU - Kanekiyo, Masaru

AU - Akahata, Wataru

AU - Xu, Ling

AU - Matsuo, Kazuhiro

AU - Natarajan, Kannan

AU - Robinson, Howard

AU - Asher, Tedi E.

AU - Price, David A.

AU - Douek, Daniel C.

AU - Margulies, David H.

AU - Nabel, Gary J.

PY - 2009/8/15

Y1 - 2009/8/15

N2 - Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8+ cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8+ T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2Dd better than the native sequences, and clones with distinct specificities were elicited by alternative vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8+ T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.

AB - Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8+ cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8+ T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2Dd better than the native sequences, and clones with distinct specificities were elicited by alternative vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8+ T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.

UR - http://www.scopus.com/inward/record.url?scp=70149088017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70149088017&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0900581

DO - 10.4049/jimmunol.0900581

M3 - Article

C2 - 19620307

AN - SCOPUS:70149088017

VL - 183

SP - 2425

EP - 2434

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -