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.
authors.affiliation: INSERM U1016, Institut Cochin, Equipe Immunologie du Diabète, Hôpital Saint-Vincent-de-Paul, 75674 Paris, Cedex 14, France.
authors.forename: Rachid
authors.initials: R
authors.lastname: Boucherma
authors.forename: Hédia
authors.initials: H
authors.lastname: Kridane-Miledi
authors.forename: Romain
authors.initials: R
authors.lastname: Bouziat
authors.forename: Michael
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Tanja
authors.initials: T
authors.lastname: Gatard
authors.forename: Francina
authors.initials: F
authors.lastname: Langa-Vives
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lemercier
authors.forename: Annick
authors.initials: A
authors.lastname: Lim
authors.forename: Marion
authors.initials: M
authors.lastname: Bérard
authors.forename: Lbachir
authors.initials: L
authors.lastname: Benmohamed
authors.forename: Søren
authors.initials: S
authors.lastname: Buus
authors.forename: Ronald
authors.initials: R
authors.lastname: Rooke
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I; D015788:HLA-A1 Antigen / Q000096:biosynthesis / Q000235:genetics; D059871:HLA-A24 Antigen / Q000096:biosynthesis / Q000235:genetics; D015796:HLA-B27 Antigen / Q000096:biosynthesis / Q000235:genetics; D015797:HLA-B35 Antigen / Q000096:biosynthesis / Q000235:genetics; D059948:HLA-B44 Antigen / Q000096:biosynthesis / Q000235:genetics; D015795:HLA-B8 Antigen / Q000096:biosynthesis / Q000235:genetics; D015236:HLA-C Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal
chemical_list: D018984:Epitopes, T-Lymphocyte; C432723:HLA-A*01:03 antigen; C438506:HLA-A*24:02 antigen; D015788:HLA-A1 Antigen; D059871:HLA-A24 Antigen; C509422:HLA-B*08:01 antigen; C464936:HLA-B*27:05 antigen; C500431:HLA-B*35:01 antigen; D015796:HLA-B27 Antigen; D015797:HLA-B35 Antigen; D059948:HLA-B44 Antigen; D015795:HLA-B8 Antigen; D015236:HLA-C Antigens; D007371:Interferon-gamma