MHC class I expression and CD8+ T cell development in TAP1/beta 2-microglobulin double mutant mice.

Ljunggren HG, Van Kaer L, Sabatine MS, Auchincloss H, Tonegawa S, Ploegh HL
Int Immunol. 1995 7 (6): 975-84

PMID: 7577806 · DOI:10.1093/intimm/7.6.975

We have bred to homozygosity gene disruptions for the transporter associated with antigen processing 1 (TAP1) and beta 2-microglobulin (beta 2m), each of which plays a distinct role in providing class I MHC subunits. Surface expression of H-2Kb or Db on cells derived from TAP1/beta 2m -/- mice was undetectable by immunofluorescence or immunoprecipitation, unlike the situation observed for TAP1 -/- and beta 2m -/- single mutant mice. Yet, TAP1/beta 2m -/- cells were able to elicit a CD8+ cytotoxic T cell (CTL) response in mice of different H-2 haplotypes and could be killed by anti-H-2b specific CTL. Furthermore, TAP1/beta 2m -/- skin grafts were rejected by bm1 mutant mice. This suggests that very low levels of conformed class I heavy chains can reach the cell surface even in the complete absence of TAP1 and beta 2m gene products, and that these molecules may select a functional CD8+ T cell repertoire. Indeed, CD4-CD8+ T cells were detected in TAP1/beta 2m -/- mice, but in numbers lower than in either of the single mutant mice. Nonetheless, it was possible to elicit a CD8+ allospecific and H-2b reactive CTL response in TAP1/beta 2m -/- mice. In line with this, TAP1/beta 2m -/- mice rapidly rejected TAP1/beta 2m +/- skin grafts. Our results suggest that some MHC class I heavy chains in TAP1/beta 2m -/- cells can reach the cell surface in a form that allows recognition by allospecific CTL and positive selection of CD8+ T cells.

MeSH Terms (16)

Animals ATP-Binding Cassette Transporters ATP Binding Cassette Transporter, Subfamily B, Member 2 beta 2-Microglobulin CD8-Positive T-Lymphocytes Crosses, Genetic Epitopes Female Histocompatibility Antigens Class I Isoantigens Lymphocyte Activation Male Mice Mice, Inbred C57BL Mice, Mutant Strains Skin Transplantation

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