Priming of immune responses against transporter associated with antigen processing (TAP)-deficient tumours: Tumour direct priming

Xiao Lin Li, Dongqing Zhang, David Knight, Yoshinobu Odaka, Jonathan Glass, James Michael Mathis, Qian Jin Zhang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We previously showed that introduction of transporter associated with antigen processing (TAP) 1 into TAP-negative CMT.64, a major histocompatibility complex class I (MHC-I) down-regulated mouse lung carcinoma cell line, enhanced T-cell immunity against TAP-deficient tumour cells. Here, we have addressed two questions: (1) whether such immunity can be further augmented by co-expression of TAP1 with B7.1 or H-2Kb genes, and (2) which T-cell priming mechanism (tumour direct priming or dendritic cell cross-priming) plays the major role in inducing an immune response against TAP-deficient tumours. We introduced the B7.1 or H-2Kb gene into TAP1-expressing CMT.64 cells and determined which gene co-expressed with TAP1 was able to provide greater protective immunity against TAP-deficient tumour cells. Our results show that immunization of mice with B7.1 and TAP1 co-expressing but not H-2Kb and TAP1 co-expressing CMT.64 cells dramatically augments T-cell-mediated immunity, as shown by an increase in survival of mice inoculated with live CMT.64 cells. In addition, our results suggest that induction of T-cell-mediated immunity against TAP-deficient tumour cells could be mainly through tumour direct priming rather than dendritic cell cross-priming as they show that T cells generated by tumour cell-lysate-loaded dendritic cells recognized TAP-deficient tumour cells much less than TAP-proficient tumour cells. These data suggest that direct priming by TAP1 and B7.1 co-expressing tumour cells is potentially a major mechanism to facilitate immune responses against TAP-deficient tumour cells.

Original languageEnglish
Pages (from-to)420-428
Number of pages9
JournalImmunology
Volume128
Issue number3
DOIs
StatePublished - 1 Nov 2009

Fingerprint

Neoplasms
T-Lymphocytes
Cross-Priming
Dendritic Cells
Immunity
Cellular Immunity
transporter associated with antigen processing (TAP)
Genes
Major Histocompatibility Complex
Immunization
Carcinoma
Cell Line
Lung

Keywords

  • B7.1
  • T cells
  • Transporter associated with antigen processing
  • Tumour immunity

Cite this

Li, Xiao Lin ; Zhang, Dongqing ; Knight, David ; Odaka, Yoshinobu ; Glass, Jonathan ; Mathis, James Michael ; Zhang, Qian Jin. / Priming of immune responses against transporter associated with antigen processing (TAP)-deficient tumours : Tumour direct priming. In: Immunology. 2009 ; Vol. 128, No. 3. pp. 420-428.
@article{064e71ef7a1c46aca10674e30fc02a60,
title = "Priming of immune responses against transporter associated with antigen processing (TAP)-deficient tumours: Tumour direct priming",
abstract = "We previously showed that introduction of transporter associated with antigen processing (TAP) 1 into TAP-negative CMT.64, a major histocompatibility complex class I (MHC-I) down-regulated mouse lung carcinoma cell line, enhanced T-cell immunity against TAP-deficient tumour cells. Here, we have addressed two questions: (1) whether such immunity can be further augmented by co-expression of TAP1 with B7.1 or H-2Kb genes, and (2) which T-cell priming mechanism (tumour direct priming or dendritic cell cross-priming) plays the major role in inducing an immune response against TAP-deficient tumours. We introduced the B7.1 or H-2Kb gene into TAP1-expressing CMT.64 cells and determined which gene co-expressed with TAP1 was able to provide greater protective immunity against TAP-deficient tumour cells. Our results show that immunization of mice with B7.1 and TAP1 co-expressing but not H-2Kb and TAP1 co-expressing CMT.64 cells dramatically augments T-cell-mediated immunity, as shown by an increase in survival of mice inoculated with live CMT.64 cells. In addition, our results suggest that induction of T-cell-mediated immunity against TAP-deficient tumour cells could be mainly through tumour direct priming rather than dendritic cell cross-priming as they show that T cells generated by tumour cell-lysate-loaded dendritic cells recognized TAP-deficient tumour cells much less than TAP-proficient tumour cells. These data suggest that direct priming by TAP1 and B7.1 co-expressing tumour cells is potentially a major mechanism to facilitate immune responses against TAP-deficient tumour cells.",
keywords = "B7.1, T cells, Transporter associated with antigen processing, Tumour immunity",
author = "Li, {Xiao Lin} and Dongqing Zhang and David Knight and Yoshinobu Odaka and Jonathan Glass and Mathis, {James Michael} and Zhang, {Qian Jin}",
year = "2009",
month = "11",
day = "1",
doi = "10.1111/j.1365-2567.2009.03127.x",
language = "English",
volume = "128",
pages = "420--428",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",

}

Priming of immune responses against transporter associated with antigen processing (TAP)-deficient tumours : Tumour direct priming. / Li, Xiao Lin; Zhang, Dongqing; Knight, David; Odaka, Yoshinobu; Glass, Jonathan; Mathis, James Michael; Zhang, Qian Jin.

In: Immunology, Vol. 128, No. 3, 01.11.2009, p. 420-428.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Priming of immune responses against transporter associated with antigen processing (TAP)-deficient tumours

T2 - Tumour direct priming

AU - Li, Xiao Lin

AU - Zhang, Dongqing

AU - Knight, David

AU - Odaka, Yoshinobu

AU - Glass, Jonathan

AU - Mathis, James Michael

AU - Zhang, Qian Jin

PY - 2009/11/1

Y1 - 2009/11/1

N2 - We previously showed that introduction of transporter associated with antigen processing (TAP) 1 into TAP-negative CMT.64, a major histocompatibility complex class I (MHC-I) down-regulated mouse lung carcinoma cell line, enhanced T-cell immunity against TAP-deficient tumour cells. Here, we have addressed two questions: (1) whether such immunity can be further augmented by co-expression of TAP1 with B7.1 or H-2Kb genes, and (2) which T-cell priming mechanism (tumour direct priming or dendritic cell cross-priming) plays the major role in inducing an immune response against TAP-deficient tumours. We introduced the B7.1 or H-2Kb gene into TAP1-expressing CMT.64 cells and determined which gene co-expressed with TAP1 was able to provide greater protective immunity against TAP-deficient tumour cells. Our results show that immunization of mice with B7.1 and TAP1 co-expressing but not H-2Kb and TAP1 co-expressing CMT.64 cells dramatically augments T-cell-mediated immunity, as shown by an increase in survival of mice inoculated with live CMT.64 cells. In addition, our results suggest that induction of T-cell-mediated immunity against TAP-deficient tumour cells could be mainly through tumour direct priming rather than dendritic cell cross-priming as they show that T cells generated by tumour cell-lysate-loaded dendritic cells recognized TAP-deficient tumour cells much less than TAP-proficient tumour cells. These data suggest that direct priming by TAP1 and B7.1 co-expressing tumour cells is potentially a major mechanism to facilitate immune responses against TAP-deficient tumour cells.

AB - We previously showed that introduction of transporter associated with antigen processing (TAP) 1 into TAP-negative CMT.64, a major histocompatibility complex class I (MHC-I) down-regulated mouse lung carcinoma cell line, enhanced T-cell immunity against TAP-deficient tumour cells. Here, we have addressed two questions: (1) whether such immunity can be further augmented by co-expression of TAP1 with B7.1 or H-2Kb genes, and (2) which T-cell priming mechanism (tumour direct priming or dendritic cell cross-priming) plays the major role in inducing an immune response against TAP-deficient tumours. We introduced the B7.1 or H-2Kb gene into TAP1-expressing CMT.64 cells and determined which gene co-expressed with TAP1 was able to provide greater protective immunity against TAP-deficient tumour cells. Our results show that immunization of mice with B7.1 and TAP1 co-expressing but not H-2Kb and TAP1 co-expressing CMT.64 cells dramatically augments T-cell-mediated immunity, as shown by an increase in survival of mice inoculated with live CMT.64 cells. In addition, our results suggest that induction of T-cell-mediated immunity against TAP-deficient tumour cells could be mainly through tumour direct priming rather than dendritic cell cross-priming as they show that T cells generated by tumour cell-lysate-loaded dendritic cells recognized TAP-deficient tumour cells much less than TAP-proficient tumour cells. These data suggest that direct priming by TAP1 and B7.1 co-expressing tumour cells is potentially a major mechanism to facilitate immune responses against TAP-deficient tumour cells.

KW - B7.1

KW - T cells

KW - Transporter associated with antigen processing

KW - Tumour immunity

UR - http://www.scopus.com/inward/record.url?scp=70349678946&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2567.2009.03127.x

DO - 10.1111/j.1365-2567.2009.03127.x

M3 - Article

C2 - 20067541

AN - SCOPUS:70349678946

VL - 128

SP - 420

EP - 428

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 3

ER -