HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice: Novel Versatile Preclinical Models of Human T Cell Responses

Rachid Boucherma; Hédia Kridane-Miledi; Romain Bouziat; Michael Rasmussen; Tanja Gatard; Francina Langa-Vives; Brigitte Lemercier; Annick Lim; Marion Bérard; Lbachir Benmohamed; Søren Buus; Ronald Rooke; François A Lemonnier

doi:10.4049/jimmunol.1300483

HLA-A01:03, HLA-A24:02, HLA-B08:01, HLA-B27:05, HLA-B35:01, HLA-B44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice: Novel Versatile Preclinical Models of Human T Cell Responses

Rachid Boucherma, Hédia Kridane-Miledi, Romain Bouziat, Michael Rasmussen, Tanja Gatard, Francina Langa-Vives, Brigitte Lemercier, Annick Lim, Marion Bérard, Lbachir Benmohamed, Søren Buus, Ronald Rooke, François A Lemonnier

24 Citationer (Scopus)

Abstract

We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with a mouse α3 domain and covalently linked to human β2-microglobulin). Whereas surface expression of several transgenes was markedly reduced in recipient mice that coexpressed endogenous H-2 class I molecules, substantial surface expression of all human transgenes was observed in mice lacking H-2 class I molecules. In these HLA monochain transgenic/H-2 class I null mice, we observed a quantitative and qualitative restoration of the peripheral CD8(+) T cell repertoire, which exhibited a TCR diversity comparable with C57BL/6 WT mice. Potent epitope-specific, HLA-restricted, IFN-γ-producing CD8(+) T cell responses were generated against known reference T cell epitopes after either peptide or DNA immunization. HLA-wise, these new transgenic strains encompass a large proportion of individuals from all major human races and ethnicities. In combination with the previously created HLA-A*02:01 and -B*07:02 transgenic mice, the novel HLA transgenic mice described in this report should be a versatile preclinical animal model that will speed up the identification and optimization of HLA-restricted CD8(+) T cell epitopes of potential interest in various autoimmune human diseases and in preclinical evaluation of T cell-based vaccines.

Originalsprog	Engelsk
Tidsskrift	Journal of immunology (Baltimore, Md. : 1950)
Vol/bind	191
Udgave nummer	2
Sider (fra-til)	583-593
Antal sider	11
DOI	https://doi.org/10.4049/jimmunol.1300483
Status	Udgivet - 15 jul. 2013

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10.4049/jimmunol.1300483

Citationsformater

Boucherma, R., Kridane-Miledi, H., Bouziat, R., Rasmussen, M., Gatard, T., Langa-Vives, F., Lemercier, B., Lim, A., Bérard, M., Benmohamed, L., Buus, S., Rooke, R., & Lemonnier, F. A. (2013). HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice: Novel Versatile Preclinical Models of Human T Cell Responses. Journal of immunology (Baltimore, Md. : 1950), 191(2), 583-593. https://doi.org/10.4049/jimmunol.1300483

HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice : Novel Versatile Preclinical Models of Human T Cell Responses. / Boucherma, Rachid; Kridane-Miledi, Hédia; Bouziat, Romain et al.

I: Journal of immunology (Baltimore, Md. : 1950), Bind 191, Nr. 2, 15.07.2013, s. 583-593.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Boucherma, R, Kridane-Miledi, H, Bouziat, R, Rasmussen, M, Gatard, T, Langa-Vives, F, Lemercier, B, Lim, A, Bérard, M, Benmohamed, L, Buus, S, Rooke, R & Lemonnier, FA 2013, 'HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice: Novel Versatile Preclinical Models of Human T Cell Responses', Journal of immunology (Baltimore, Md. : 1950), bind 191, nr. 2, s. 583-593. https://doi.org/10.4049/jimmunol.1300483

Boucherma R, Kridane-Miledi H, Bouziat R, Rasmussen M, Gatard T, Langa-Vives F et al. HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice: Novel Versatile Preclinical Models of Human T Cell Responses. Journal of immunology (Baltimore, Md. : 1950). 2013 jul. 15;191(2):583-593. doi: 10.4049/jimmunol.1300483

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title = "HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice: Novel Versatile Preclinical Models of Human T Cell Responses",

abstract = "We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with a mouse α3 domain and covalently linked to human β2-microglobulin). Whereas surface expression of several transgenes was markedly reduced in recipient mice that coexpressed endogenous H-2 class I molecules, substantial surface expression of all human transgenes was observed in mice lacking H-2 class I molecules. In these HLA monochain transgenic/H-2 class I null mice, we observed a quantitative and qualitative restoration of the peripheral CD8(+) T cell repertoire, which exhibited a TCR diversity comparable with C57BL/6 WT mice. Potent epitope-specific, HLA-restricted, IFN-γ-producing CD8(+) T cell responses were generated against known reference T cell epitopes after either peptide or DNA immunization. HLA-wise, these new transgenic strains encompass a large proportion of individuals from all major human races and ethnicities. In combination with the previously created HLA-A*02:01 and -B*07:02 transgenic mice, the novel HLA transgenic mice described in this report should be a versatile preclinical animal model that will speed up the identification and optimization of HLA-restricted CD8(+) T cell epitopes of potential interest in various autoimmune human diseases and in preclinical evaluation of T cell-based vaccines.",

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T1 - HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice

T2 - Novel Versatile Preclinical Models of Human T Cell Responses

AU - Boucherma, Rachid

AU - Kridane-Miledi, Hédia

AU - Bouziat, Romain

AU - Rasmussen, Michael

AU - Gatard, Tanja

AU - Langa-Vives, Francina

AU - Lemercier, Brigitte

AU - Lim, Annick

AU - Bérard, Marion

AU - Benmohamed, Lbachir

AU - Buus, Søren

AU - Rooke, Ronald

AU - Lemonnier, François A

PY - 2013/7/15

Y1 - 2013/7/15

N2 - We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with a mouse α3 domain and covalently linked to human β2-microglobulin). Whereas surface expression of several transgenes was markedly reduced in recipient mice that coexpressed endogenous H-2 class I molecules, substantial surface expression of all human transgenes was observed in mice lacking H-2 class I molecules. In these HLA monochain transgenic/H-2 class I null mice, we observed a quantitative and qualitative restoration of the peripheral CD8(+) T cell repertoire, which exhibited a TCR diversity comparable with C57BL/6 WT mice. Potent epitope-specific, HLA-restricted, IFN-γ-producing CD8(+) T cell responses were generated against known reference T cell epitopes after either peptide or DNA immunization. HLA-wise, these new transgenic strains encompass a large proportion of individuals from all major human races and ethnicities. In combination with the previously created HLA-A*02:01 and -B*07:02 transgenic mice, the novel HLA transgenic mice described in this report should be a versatile preclinical animal model that will speed up the identification and optimization of HLA-restricted CD8(+) T cell epitopes of potential interest in various autoimmune human diseases and in preclinical evaluation of T cell-based vaccines.

AB - We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with a mouse α3 domain and covalently linked to human β2-microglobulin). Whereas surface expression of several transgenes was markedly reduced in recipient mice that coexpressed endogenous H-2 class I molecules, substantial surface expression of all human transgenes was observed in mice lacking H-2 class I molecules. In these HLA monochain transgenic/H-2 class I null mice, we observed a quantitative and qualitative restoration of the peripheral CD8(+) T cell repertoire, which exhibited a TCR diversity comparable with C57BL/6 WT mice. Potent epitope-specific, HLA-restricted, IFN-γ-producing CD8(+) T cell responses were generated against known reference T cell epitopes after either peptide or DNA immunization. HLA-wise, these new transgenic strains encompass a large proportion of individuals from all major human races and ethnicities. In combination with the previously created HLA-A*02:01 and -B*07:02 transgenic mice, the novel HLA transgenic mice described in this report should be a versatile preclinical animal model that will speed up the identification and optimization of HLA-restricted CD8(+) T cell epitopes of potential interest in various autoimmune human diseases and in preclinical evaluation of T cell-based vaccines.

U2 - 10.4049/jimmunol.1300483

DO - 10.4049/jimmunol.1300483

M3 - Journal article

C2 - 23776170

SN - 0022-1767

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JO - Journal of Immunology

JF - Journal of Immunology

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ER -