Expression and function of HLA‐A2.1 in transgenic mice

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Abstract
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 β2‐microglobulin (β2m), confirming that HLA‐A2 does not require human β2m 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‐β2m‐associated HLA heavy chain inside the cell. In contrast the amount of HLA: β2m complex is low. Thus, in transgenic mice HLA‐A2 seems to compete poorly with H‐2 heavy chains for mouse β2m.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”.