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HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice.

TitleHLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice.
Publication TypeJournal Article
Year of Publication1997
AuthorsPascolo S, Bervas N, Ure JM, Smith AG, Lemonnier FA, Pérarnau B
JournalJ Exp Med
Volume185
Issue12
Pagination2043-51
Date Published1997 Jun 16
ISSN0022-1007
KeywordsAnimals, beta 2-Microglobulin, Cytotoxicity, Immunologic, H-2 Antigens, Histocompatibility Antigen H-2D, HLA-A2 Antigen, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, T-Lymphocytes, Cytotoxic
Abstract

Three different HLA-A2.1 monochains were engineered in which either the human or mouse beta2-microglobulin (beta2m) is covalently linked to the NH2 terminus of the heavy chain by a 15- amino acid long peptide: HHH, entirely human, HHD, with the mouse H-2Db alpha3, transmembrane, and cytoplasmic domains, and MHD, homologous to HHD but linked to the mouse beta2mb. The cell surface expression and immunological capacities of the three monochains were compared with transfected cells, and the selected HHD construct was introduced by transgenesis in H-2Db-/- beta2m-/- double knockout mice. Expression of this monochain restores a sizable peripheral CD8(+) T cell repertoire essentially educated on the transgenic human molecule. Consequently, infected HHD, H-2Db-/- beta2m-/- mice generate only HLA-A2.1-restricted CD8(+) CTL responses against influenza A and vaccinia viruses. Interestingly, the CTL response to influenza A virus is mostly, if not exclusively, directed to the 58-66 matrix peptide which is the HLA-A2.1-restricted immunodominant epitope in humans. Such mice might constitute a versatile animal model for the study of HLA-A2.1-restricted CTL responses of vaccine interest.

Alternate JournalJ. Exp. Med.
PubMed ID9182675
PubMed Central IDPMC2196346