Expression and function of HLA-A2.1 in transgenic mice.
We have derived a number of transgenic mouse lines which express the human major histocompatibility complex class I gene HLA-A2.1. Two lines carry the complete human HLA-A2.1, the others bear a recombinant gene in which the HLA-A2.1 coding regions are fused to the H-2Kb promoter. Analysis of transgenic spleen cells by immunofluorescence demonstrates that these mouse cells express HLA-A2.1 on their surface in association with mouse beta 2-microglobulin (beta 2m), confirming that HLA-A2 does not require human beta 2m to be expressed at the cell surface. The cells contain more HLA mRNA than endogenous H-2 class I mRNA. There is also a large pool of non-beta 2m-associated HLA heavy chain inside the cell. In contrast the amount of HLA:beta 2m complex is low. Thus, in transgenic mice HLA-A2 seems to compete poorly with H-2 heavy chains for mouse beta 2m. The HLA-A2.1 transgenic mice do not produce influenza-virus-specific cytotoxic T cells (CTL) restricted to the HLA transgene, at least in sufficient numbers to be measured in a direct bulk CTL assay. The dominance of H-2-restricted clones may be the result of quantitative rather than qualitative factors. However, HLA-A2.1 transgenic spleen cells are effective in stimulating an allogeneic CTL response in normal mice. This response is not H-2 restricted. Cold target inhibition studies show that there are at least two populations of CTL, one of which is specific for HLA-A2.1 on mouse cells. This result suggests that at least some allo-CTL are directed against major histocompatibility complex plus "self-peptide".
Epstein
H
H
Department of Pathology, Cambridge University.
Hardy
R
R
May
J S
JS
Johnson
M H
MH
Holmes
N
N
D000818:Animals; D015152:Blotting, Northern; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005796:Genes; D006183:H-2 Antigens / Q000235:genetics; D015789:HLA-A2 Antigen / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D006183:H-2 Antigens; D015789:HLA-A2 Antigen; D012333:RNA, Messenger